Follicular LymphomaPhase 1/2ROMULUSNCT01691898
A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)
A Phase 1/2 study testing Obinutuzumab, Pinatuzumab Vedotin and Polatuzumab Vedotin in people with Follicular Lymphoma and Diffuse Large B-Cell Lymphoma, run by Genentech, Inc. at 41 sites in 6 countries.
Trial summary
This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma, Diffuse Large B-Cell Lymphoma
- What is being tested?
- Obinutuzumab, Pinatuzumab Vedotin and Polatuzumab Vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 231 participants
- Where
- 41 sitesin 6 countries
- Study dates
- 27 Sep 2012to 7 Feb 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
- Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
- Have a clinical indication for treatment as determined by the investigator
- Must have at least one bi-dimensionally measurable lesion (greater than [>] 1.5 centimeters [cm] in its largest dimension by CT scan or Magnetic Resonance Imaging [MRI])
Who cannot join
- Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
- Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (</=) 2 prior study start
- Completion of autologous stem cell transplant (SCT) within 100 days prior study start
- Prior allogeneic SCT
- Eligibility for autologous SCT (participants with r/r DLBCL)
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- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Current or past history of central nervous system lymphoma
- Current Grade >1 peripheral neuropathy
- Vaccination with a live vaccine within 28 days prior to treatment
Trial locations and contacts
41 sites in 6 countries.
41 sites in 6 countries
United States26 sites
Univ of Michigan Med School; Hematology Oncology
Ann Arbor, Michigan, 48109
Roswell Park Cancer Inst.
Buffalo, New York, 14263
Oncology Hematology Care Inc
Cincinnati, Ohio, 45242
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, 75246
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, 80218
Willamette Valley Cancer Ctr - 520 Country Club
Eugene, Oregon, 97401-8122
Fairfax N Virginia Hem/Onc PC
Fairfax, Virginia, 22031
Florida Cancer Specialists - Fort Myers (Colonial Center Dr)
Fort Myers, Florida, 33905
Comprehensive Cancer Centers of Nevada - Eastern Avenue
Las Vegas, Nevada, 89169
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Univ of Wisconsin-Madison
Madison, Wisconsin, 53705
Hematology Oncology Associates; Carol G. Simon Ctr
Morristown, New Jersey, 07960
Regional Cancer Care Associates LLC - Morristown
Morristown, New Jersey, 07962
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
Nashville, Tennessee, 37203
New York University Cancer Cen
New York, New York, 10016
Oregon Health Sciences Uni
Portland, Oregon, 97239
Oncology & Hematolgy Associates of SW Va Inc. - Roanoke
Roanoke, Virginia, 24014
Cancer Care Centers of South Texas
San Antonio, Texas, 78217
Texas Transplant Inst.
San Antonio, Texas, 78229
Florida Cancer Specialists; Sarasota
Sarasota, Florida, 34232
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Stanford Cancer Center
Stanford, California, 94305-5820
Texas Oncology, P.A. - Tyler; Tyler Cancer Center
Tyler, Texas, 75702
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, 98684
Georgetown University Medical Center Lombardi Cancer Center
Washington D.C., District of Columbia, 20007
Yakima Valley Memorial Hospital/North Star Lodge
Yakima, Washington, 98902
France5 sites
Hopital Claude Huriez - CHU Lille
Lille, 59037
CHU Montpellier - Saint ELOI
Montpellier, 34295
Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)
Paris, 75475
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Centre Henri Becquerel; Hematologie
Rouen, 76038
Canada3 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
Montreal, Quebec, H3T 1E2
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 1H6
Germany3 sites
Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
Heidelberg, 69120
Universitätsmedizin Johannes Gutenberg Universität; Klinik u. Poliklinik f. Neurologie
Mainz, 55131
Klinikum d.Universität München Campus Großhadern
München, 81377
Italy3 sites
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
Bologna, Emilia-Romagna, 40138
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
Milan, Lombardy, 20133
Azienda Ospedale San Giovanni
Turin, Piedmont, 10126
Netherlands1 site
Academisch Medisch Centrum; Hematologie
Amsterdam, 1105 AZ
About this study
Official title: A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of Pinatuzumab Vedotin (DCDT2980S) in Combination With Rituximab or Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab and a Non-Randomized Phase Ib/II Evaluation of Polatuzumab Vedotin in Combination With Obinutuzumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).
- Conditions
- Follicular Lymphoma, Diffuse Large B-Cell Lymphoma
- Being tested
- Obinutuzumab, Pinatuzumab Vedotin, Polatuzumab Vedotin, Rituximab
- Medical subject headings
- Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObinutuzumabDrug
Also called GA101, Gazyva, Gazyvaro
Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.
Pinatuzumab VedotinDrug
Also called DCDT2980S
Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.
Polatuzumab VedotinDrug
Also called DCDS4501A
Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.
RituximabDrug
Also called MabThera/Rituxan
RTX 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab | Experimental | For the first 2 cycles, RTX 375 milligrams per square meter (mg/m^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule). Receives: Drug: Pinatuzumab Vedotin; Drug: Polatuzumab Vedotin; Drug: Rituximab |
| Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab | Experimental | For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule). Receives: Drug: Pinatuzumab Vedotin; Drug: Polatuzumab Vedotin; Drug: Rituximab |
| Cohort C (FL): RTX + Polatuzumab | Experimental | For the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study. Receives: Drug: Polatuzumab Vedotin; Drug: Rituximab |
| Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab | Experimental | For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study. Receives: Drug: Obinutuzumab; Drug: Polatuzumab Vedotin |
| Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab | Experimental | For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study. Receives: Drug: Obinutuzumab; Drug: Polatuzumab Vedotin |
| Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab | Experimental | For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study. Receives: Drug: Obinutuzumab; Drug: Polatuzumab Vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments greater than or equal to (>/=) 4 weeks after initial documentation. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50 percent (%) decrease in sum of the products of greatest diameters (SPD) of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. Participants with insufficient data to determine response were classified as non-responders.
Measured: Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)
Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014). DOR was defined as the time from the initial documentation of a CR or PR to the time of PD or death. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
Measured: First occurrence of objective response up to PD/relapse or death due to any cause, whichever occurred first (up to approximately 3.5 years)
Percentage of Participants With CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) Per Lugano 2014 Response Criteria: Cohorts E, G, and H
Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Secondary outcomes (49)
Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin
Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against pinatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.
Measured: Baseline, post-baseline (up to approximately 5.5 years)
Number of Participants With ADA to Polatuzumab Vedotin
Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against polatuzumab vedotin at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.
Measured: Baseline, post-baseline (up to approximately 5.5 years)
Number of Participants With ADA to Obinutuzumab
Participants provided blood samples for evaluation of ADA. The number of participants with positive results for ADA against obinutuzumab at Baseline and at any of the post-baseline assessment time-points (overall 1.5 years) was reported. Participants positive at any post-baseline time points were post-baseline evaluable participants determined to have "Treatment-induced ADAs" or "Treatment-enhanced ADA" during the study period. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result.
Measured: Baseline, post-baseline (up to approximately 5.5 years)
Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Percentage of Participants Who Died Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)
Percentage of participants who died due to any cause was reported.
Measured: Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C)
OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
Measured: Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR was defined as a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by the Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT scan. OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR was defined as a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. CR was defined as reduction of longest transverse diameter (LDi) of target nodes/nodal masses to less than or equal to (</=) 1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. CR was defined as reduction of LDi of target nodes/nodal masses to </=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Tumor response assessment was performed by an IRC according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to </=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. PR was defined as >/=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen by at least >50% beyond normal; and no new lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Tumor response assessment was performed by investigator according to modified Lugano classification using CT scan. OR was defined as a response of CR or PR. CR was defined as reduction of LDi of target nodes/nodal masses to </=1.5 cm, no extralymphatic sites of disease, absence of non-measured lesions and new lesions, reduction of enlarged organs to normal, and normal/IHC-negative bone marrow morphology. PR was defined as >/=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen by at least >50% beyond normal; and no new lesions. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With Best OR Based on PET/CT or CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Tumor response assessment was performed by investigator according to modified Lugano classification using PET/CT or CT scan. Best OR was defined as a response of CR or PR. CR was defined as a score of 1 (no uptake above background), 2 (uptake </=mediastinum), or 3 (uptake <mediastinum but </=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. PR was defined as a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites; no new lesions; and reduced residual uptake in bone marrow compared with baseline. 90% CI for percentage of responders was calculated using Clopper-Pearson method.
Measured: Baseline up to disease progression or death, whichever occurred first (up to approximately 5.5 years)
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
AUCinf for rituximab was estimated from serum concentration data using non-compartmental analysis.
Measured: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Maximum Observed Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Cmax for rituximab was estimated from serum concentration data using non-compartmental analysis.
Measured: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
CL for rituximab was estimated from serum concentration data using non-compartmental analysis.
Measured: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
t1/2 for rituximab was estimated from serum concentration data using non-compartmental analysis.
Time Frame: Pre-infusion (Hour 0) \& 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, \& 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days).
Measured: Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description)
Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Vss for rituximab was estimated from serum concentration data using non-compartmental analysis.
Time Frame: Pre-infusion (Hour 0) \& 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1-4 and every 4th Cycle thereafter (approximately up to 1.5 years); Day 8, Day 15 of Cycle 1 and 3; 30 Days after last infusion; 2, 4, \& 6 months after treatment completion visit (approximately up to 1.5 years, Cycle length= 21 days)
Measured: Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description)
AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
AUCinf of total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with Monomethyl Auristatin E (MMAE)-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
AUCinf of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. Antibody conjugated MMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Area Under the Concentration-Time Curve From Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
AUClast of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Cmax of total antibody for pinatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Cmax of acMMAE for pinatuzumab was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Cmax of unconjugated MMAE was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
AUCinf of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
AUCinf of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
AUClast of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
Cmax of total antibody for polatuzumab vedotin was estimated from serum concentration data using non-compartmental analysis. Total antibody is defined as antibody with MMAE-to-antibody ratio equal or greater than zero, including fully conjugated, partially unconjugated, and fully unconjugated antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
Cmax of acMMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. acMMAE is the total concentration of MMAE that was conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
Cmax of Unconjugated MMAE for polatuzumab vedotin was estimated from plasma concentration data using non-compartmental analysis. Unconjugated MMAE is the total concentration of MMAE that was not conjugated to the antibody.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Obinutuzumab: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Cmax of obinutuzumab was estimated from serum concentration data using non-compartmental analysis.
Measured: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Overall Survival (OS): Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
OS was defined as the time from the date of randomization or enrollment to the date of death from any cause. The median OS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
Measured: Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Percentage of Participants Who Died Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)
Percentage of participants who died due to any cause was reported.
Measured: Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node. PFS was defined as the time from the date of randomization to the date of PD or death from any cause, whichever occurred first. In absence of PD or death, PFS was censored at the date of the last tumor assessment. Participants with no post-baseline tumor assessment were censored on the date of randomization or date of enrollment. The median PFS was estimated using Kaplan-Meier estimates and the 95% CI for median was computed using the method of Brookmeyer and Crowley.
Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Obinutuzumab Containing Cohorts (Cohorts E + H and E + G)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments >/=4 weeks after initial documentation. PD was defined as appearance of any new lesion more than 1.5 cm in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
Measured: Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 5.5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2012 (estimated)
- Study start27 Sep 2012
- Primary completion8 Mar 2017
- Study completion7 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 231 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01691898
- Sponsor's protocol ID
- GO27834
- Other IDs
- 2011-004377-84
- Acronym
- ROMULUS
- Status last verified
- Feb 2020
- First submitted
- 16 Sep 2012
- Last updated
- 21 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
PubMed 32770353Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
PubMed 32705923Morschhauser F, Flinn IW, Advani R, Sehn LH, Diefenbach C, Kolibaba K, Press OW, Salles G, Tilly H, Chen AI, Assouline S, Cheson BD, Dreyling M, Hagenbeek A, Zinzani PL, Jones S, Cheng J, Lu D, Penuel E, Hirata J, Wenger M, Chu YW, Sharman J. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019 May;6(5):e254-e265. doi: 10.1016/S2352-3026(19)30026-2. Epub 2019 Mar 29.
PubMed 30935953
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of Pinatuzumab Vedotin (DCDT2980S) in Combination With Rituximab or Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab and a Non-Randomized Phase Ib/II Evaluation of Polatuzumab Vedotin in Combination With Obinutuzumab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT01691898
- Acronym / sponsor ID
- ROMULUS / GO27834
- Conditions
- Follicular Lymphoma, Diffuse Large B-Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 231 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Sep 2012 (actual)
- Primary completion
- 8 Mar 2017 (actual)
- Study completion
- 7 Feb 2019 (actual)
- First posted
- 25 Sep 2012 (estimated)
- Results
- Posted 19 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab | Experimental | Drug: Pinatuzumab Vedotin, Drug: Polatuzumab Vedotin, Drug: RituximabFor the first 2 cycles, RTX 375 milligrams per square meter (mg/m^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule). |
| Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab | Experimental | Drug: Pinatuzumab Vedotin, Drug: Polatuzumab Vedotin, Drug: RituximabFor the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule). |
| Cohort C (FL): RTX + Polatuzumab | Experimental | Drug: Polatuzumab Vedotin, Drug: RituximabFor the first 2 cycles, RTX 375 mg/m^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study. |
| Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab | Experimental | Drug: Obinutuzumab, Drug: Polatuzumab VedotinFor the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study. |
| Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab | Experimental | Drug: Obinutuzumab, Drug: Polatuzumab VedotinFor the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study. |
| Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab | Experimental | Drug: Obinutuzumab, Drug: Polatuzumab VedotinFor the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
- Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
- Have a clinical indication for treatment as determined by the investigator
Key exclusion criteria (11 listed)
- Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
- Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
- Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (</=) 2 prior study start
- Completion of autologous stem cell transplant (SCT) within 100 days prior study start
- Prior allogeneic SCT
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObinutuzumabAlso: GA101, Gazyva, GazyvaroObinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles. | Drug | Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab, Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab, Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab |
| Pinatuzumab VedotinAlso: DCDT2980SPinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle. | Drug | Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab, Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab |
| Polatuzumab VedotinAlso: DCDS4501APolatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle. | Drug | Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab, Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab, Cohort C (FL): RTX + Polatuzumab, Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab, Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab, Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab |
| RituximabAlso: MabThera/RituxanRTX 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle. | Drug | Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab, Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab, Cohort C (FL): RTX + Polatuzumab |
Primary outcome
Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014) and confirmed by repeat assessments greater than or equal to (>/=) 4 weeks after initial documentation. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50 percent (%) decrease in sum of the products of greatest diameters (SPD) of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. Participants with insufficient data to determine response were classified as non-responders.
Duration of Objective Response (DOR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: First occurrence of objective response up to PD/relapse or death due to any cause, whichever occurred first (up to approximately 3.5 years)
Tumor response was evaluated according to modified response and progression criteria for NHL published by Cheson et al (2007 and 2014). DOR was defined as the time from the initial documentation of a CR or PR to the time of PD or death. CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as >/=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >/=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. PD was defined as appearance of any new lesion more than 1.5 centimeters (cm) in any axis, at least a 50% increase from nadir in the SPD or longest diameter of any previous lesion or node.
Percentage of Participants With CR at End of Treatment (EOT) Based on Positron Emission Tomographic/Computed Tomography (PET/CT) Assessment Determined by Independent Review Committee (IRC) Per Lugano 2014 Response Criteria: Cohorts E, G, and H
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Tumor response assessment was performed by an IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to [</=] mediastinum), or 3 (uptake less than [<] mediastinum but </=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.
49 secondary outcomes
Number of Participants With Anti-Drug Antibodies (ADA) to Pinatuzumab Vedotin
Time frame: Baseline, post-baseline (up to approximately 5.5 years)
Number of Participants With ADA to Polatuzumab Vedotin
Time frame: Baseline, post-baseline (up to approximately 5.5 years)
Number of Participants With ADA to Obinutuzumab
Time frame: Baseline, post-baseline (up to approximately 5.5 years)
Percentage of Participants With PD as Determined by Modified Response and Progression Criteria for NHL or Death Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Progression-free Survival (PFS) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 5.5 years)
Percentage of Participants Who Died Due to Any Cause: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Overall Survival (OS): Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Baseline up to death due to any cause (from baseline up to study completion date, up to approximately 5.5 years)
Percentage of Participants With CR at EOT Based on PET/CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on PET/CT Assessment as Determined by the Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With CR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by IRC Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With OR at EOT Based on CT Assessment Alone as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E + H and E + G)
Time frame: 6-8 weeks after Cycle 8 Day 1 (cycle length = 21 Days) or last study treatment (maximum up to 27-29 weeks)
Percentage of Participants With Best OR Based on PET/CT or CT Assessment as Determined by Investigator Per Lugano 2014 Response Criteria: Obinutuzumab-Containing Cohorts (Cohorts E, G, and H)
Time frame: Baseline up to disease progression or death, whichever occurred first (up to approximately 5.5 years)
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Maximum Observed Concentration (Cmax) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Systemic Clearance (CL) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Pre-infusion (Hour 0) & 30 minutes post-infusion (infusion length= 2-6 hours) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 days)
Half-Life (t1/2) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description)
Volume of Distribution at Steady State (Vss) of Rituximab: Rituximab Containing Regimens (Arms A and B, Cohort C)
Time frame: Day 1 up to 1.5 years (detailed timeframe is provided in the Outcome Measure Description)
AUCinf of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Antibody Conjugated Monomethyl Auristatin E (acMMAE) for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Area Under the Concentration-Time Curve From Time Zero To Last Measurable Concentration (AUClast) of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Pinatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 2.4 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUClast of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Cmax of Unconjugated MMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Rituximab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of Total Antibody for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
AUCinf of acMMAE for Polatuzumab Vedotin at Dose Level 1.8 mg/kg Given in Combination With Obinutuzumab
Time frame: Pre-infusion (Hour 0) & 30 minutes Post-infusion (infusion length=30-90 minutes) on Day 1 of Cycle 1; Day 8, Day 15 of Cycle 1 (Cycle length= 21 Days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32770353Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.
- Derived from this study: PubMed 32705923Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.
- Derived from this study: PubMed 30935953Morschhauser F, Flinn IW, Advani R, Sehn LH, Diefenbach C, Kolibaba K, Press OW, Salles G, Tilly H, Chen AI, Assouline S, Cheson BD, Dreyling M, Hagenbeek A, Zinzani PL, Jones S, Cheng J, Lu D, Penuel E, Hirata J, Wenger M, Chu YW, Sharman J. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019 May;6(5):e254-e265. doi: 10.1016/S2352-3026(19)30026-2. Epub 2019 Mar 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Genentech, Inc.
41 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Obinutuzumab, Pinatuzumab Vedotin and Polatuzumab Vedotin in people with Follicular Lymphoma and Diffuse Large B-Cell Lymphoma, run by Genentech, Inc. at 41 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, France, Canada, Germany, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With a Best Overall Response (OR) of Complete Response (CR) or Partial Response (PR) as Determined by Modified Response and Progression Criteria for NHL: Rituximab Containing Regimens (Arms A and B, Cohort C) (time frame: Baseline up to 12 months after the last dose of study treatment (up to approximately 3.5 years)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01691898, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2020.