Diffuse Large B-cell LymphomaPhase 1NCT03255096
A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6
A Phase 1 study testing RO6870810, Venetoclax and Rituximab in people with Diffuse Large B-cell Lymphoma and High-Grade B-cell Lymphoma, run by Hoffmann-La Roche at 9 sites in 4 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, High-Grade B-cell Lymphoma
- What is being tested?
- RO6870810, Venetoclax and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 28 Aug 2017to 3 Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Life expectancy >3 months as per investigator's assessment.
- Part 1 and Part 2 Group 1: Participantts with diffuse large B-cell lymphoma (DLBCL) relapsed or refractory to ≥ 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for autologous stem cell transplantation (ASCT) (including due to chemorefractory disease). Participants with transformed FL are eligible, provided DLBCL or HGBL-DH/TH histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. The Sponsor retains the option to limit the number of participants enrolled with transformed FL.
- Part 2, Group 2: Patients identified with DE-DLBCL (expression MYC ≥40%, BCL2 > 50%) and or HGBL-DH/TH, relapsed or refractory to >= 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for ASCT (including due to chemorefractory disease). Patients with transformed follicular lymphoma (FL) are eligible, provided DE-DLBCL and/or HGBL-DH/TH histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. The Sponsor retains the option to limit the number of participants enrolled with transformed FL.
- Part 1 and Part 2: Willing to provide the protocol specified tumor biopsy(ies): at screening a fresh biopsy (if no archival biopsy tissue of less than 3 months prior to treatment and without intercurrent treatment is available); Part 2: Willing to provide an additional biopsy on Cycle 2 Day 15 (+ 2 days).
- Acceptable liver function, as specified below:
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- Total bilirubin ≤ 2 times upper limit of normal (ULN). (Participants with known Gilbert's disease who has serum bilirubin ≤ 3 × ULN may be enrolled).
- Aspartate transaminase (AST; SGOT), alanine transaminase (ALT; SGPT) ≤ 2.5 × ULN, (or ≤ 5 × ULN if tumor involvement (liver) is present).
- Gamma-glutamyl transferase (GGT) alkaline phosphatase ≤ 2.5 × ULN.
- Acceptable renal function, as specified below:
- Creatinine clearance (CrCl) calculated by Cockroft-Gault formula of ≥ 60 mL/min.
- Acceptable hematologic status (growth factors cannot be used within the previous 7 days), as specified below:
- Absolute neutrophil count (ANC) ≥ 1000 cells/μL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 75,000 (platelets/μL)
- Uncontrolled symptomatic hypercalcemia.
- Acceptable coagulation status, as specified below:
- Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.2 × ULN (unless receiving anticoagulation therapy, if receiving anticoagulation therapy, eligibility will be based upon international normalized ratio [INR]).
- INR ≤ 1.6 (unless receiving anticoagulation therapy).
- If receiving warfarin: INR ≤ 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy).
- Acceptable method of contraception
Who cannot join
- Current central nervous system (CNS) lymphoma or leptomeningeal infiltration.
- New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, within the past 6 months, unstable arrhythmia, or known pericardial disease.
- Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome.
- Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator would preclude safe participation in the study.
- Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
- Clinically important respiratory impairment
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- Grade ≥ 3 sensory or motor neuropathy.
- Any Grade >1 (according to the NCI CTCAE 4.03) adverse reaction unresolved from previous treatments and not readily managed and controlled with supportive care.
- Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
- History of progressive multifocal leukoencephalopathy (PML).
- History of other malignancy within 2 years prior to screening, except for ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score ≤ 7) not requiring treatment or appropriately treated Stage I uterine cancer.
- Completion of ASCT within 100 days prior to Day 1 of Cycle1.
- Prior standard or investigational anti-cancer therapy, as specified below:
- Radio-immunoconjugate 4 weeks or 5 half-lives, whichever is longer prior to Day 1 of Cycle 1.
- Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 3 weeks prior to Day 1 of Cycle 1.
- Radiotherapy, chemotherapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1.
- CAR T-cell therapy 30 days prior to Day 1 of Cycle 1.
- History of major solid organ transplant (i.e., heart, lungs, liver and kidney).
- History of an allogeneic bone marrow transplant.
- Major surgical procedure within 28 days prior to Day 1 of Cycle 1.
- Treatment with systemic corticosteroids ≥ 20 mg/day prednisone or equivalent, for non-lymphoma treatment reasons. For lower acceptable doses, documentation of a stable dose for at least 4 weeks prior to Day 1 of Cycle 1 is required.
- 18. Treatment with strong to moderate CYP3A inhibitors or moderate CYP3A inducers within 7 days prior to the first dose of study treatment.
- Treatment with strong CYP3A inducers within 14 days prior to the first dose of study treatment of RO6870810/venetoclax.
- Consumption of grapefruits, grapefruit products, Seville oranges (including marmalade that contains Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax.
- Participants who are currently receiving any other investigational agent ((other than anti-cancer therapy as specified in exclusion criteria number 13) or have received an investigational agent within 30 days or 5 half-lives prior to Day 1 of Cycle 1, whichever is longer.
- Prior treatment with small molecule bromodomain and extra terminal (BET) family inhibitor.
- Known to be human immunodeficiency virus (HIV) positive.
- Presence of positive test results for hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HcAb) (for participants receiving regimen including rituximab)
- Pregnant or breastfeeding female.
- Significant allergy to a biological pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the participant.
- Uncontrolled cancer pain. Participants requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrollment.
- History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies (for participants receiving regimen including rituximab).
- Known sensitivity or allergy to murine products or any component of RO6870810, venetoclax, or rituximab.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
United States4 sites
Levine Cancer Institute - Blythe
Charlotte, North Carolina, 28203
City of Hope National Medical Center
Duarte, California, 91010
Weill Cornell Medical College
New York, New York, 10065
Stanford Cancer Center
Stanford, California, 94305-5820
Spain3 sites
Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
Barcelona, 08025
Hospital Duran i Reynals; Servicio de Hematologia
Barcelona, 08907
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
Madrid, 28040
Australia1 site
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, 3000
About this study
Official title: Open-Label, Dose Escalation/Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and/or High-Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 Gene Rearrangements
The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).
- Being tested
- RO6870810, Venetoclax, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO6870810Drug
RO6870810 subcutaneously (SC) at dose of 0.30, 0.45, or 0.65 milligram per kilogram (mg/kg) on Days 1-14 of 21-day cycles.
VenetoclaxDrug
Venetoclax tablets orally at dose of 400 mg once daily (QD) continuously for 21 days.
RituximabDrug
Rituximab intravenously (IV) at dose of 375 mg/m^2 weekly during the first 21-day cycle (C1) and on day 1 of each cycle thereafter.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase (Part 1) | Experimental | Participants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Receives: Drug: RO6870810; Drug: Venetoclax; Drug: Rituximab |
| Expansion Phase (Part 2) | Experimental | Participants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. Receives: Drug: RO6870810; Drug: Venetoclax; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose-Limiting Toxiciities (DLT)- Part 1
DLT is defined as any of the toxicities- occurs within the first cycle for which the participant receives the full intended combination doses and number of administrations; is considered to be related to study treatment by the investigator; is not attributed to disease progression or another clearly identifiable cause.
Measured: Cycle (C) 1 (21 days)
Percentage of Participants With Adverse Events (AEs) - Part 1
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: Up to 36 months
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 1
Measured: Up to 36 months
Complete Response (CR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- Recommended Dose (RD) Expansion - Part 2
Measured: Up to 36 months
Overall Response (OR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- RD Expansion - Part 2
Measured: Up to 36 months
Secondary outcomes (19)
Percentage of Participants With Adverse Events (AEs) - Part 2
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: Up to 36 months
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 2
Measured: Up to 36 months
Maximum Concentration (Cmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Trough Serum Concentration (Cmin) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Cycle 2 and all other subsequent even Cycles (Up to 36 months)
Time of Maximum Concentration (tmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Clearance (CL) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Volume of Distribution (Vd) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Area Under the Curve (AUC) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Complete Response (CR) Rate as Determined by the Investigator Based on the Modified Lugano Response Criteria- Part 1 and Part 2
Measured: Up to 36 months
Complete Response (CR) Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2
Measured: Up to 36 months
Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of Modified Lugano Response Criteria- Part 1 and Part 2
Measured: Up to 36 months
Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2
Measured: Up to 36 months
Duration of Response (DoR)- Part 1 and Part 2
Measured: Up to 36 months
Progression-Free Survival (PFS)- Part 1 and Part 2
Measured: Up to 36 months
Event-Free Survival (EFS)- Part 1 and Part 2
Measured: Up to 36 months
Disease-Free Survival (DFS)- Part 1 and Part 2
Measured: Up to 36 months
Overall Survival (OS)- Part 1 and Part 2
Measured: Up to 36 months
Half-Life (t1/2) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Measured: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Percentage of Ant-Drug Antibodies (ADA) Against Rituximab - Part 1 and Part 2
Measured: Pre-dose, End of Infusion Day 1 Cycle 1; Pre-dose Day 1 Cycle 2, 3, 4 , 6 and all other even Cycles (Up to 36 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start28 Aug 2017
- Primary completion3 Jul 2019
- Study completion3 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255096
- Sponsor's protocol ID
- NP39461
- Other IDs
- 2017-000357-39, 2017
- Status last verified
- Jan 2022
- First submitted
- 31 Jul 2017
- Last updated
- 24 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Dickinson M, Briones J, Herrera AF, Gonzalez-Barca E, Ghosh N, Cordoba R, Rutherford SC, Bournazou E, Labriola-Tompkins E, Franjkovic I, Chesne E, Brouwer-Visser J, Lechner K, Brennan B, Nuesch E, DeMario M, Ruttinger D, Kornacker M, Hutchings M. Phase 1b study of the BET protein inhibitor RO6870810 with venetoclax and rituximab in patients with diffuse large B-cell lymphoma. Blood Adv. 2021 Nov 23;5(22):4762-4770. doi: 10.1182/bloodadvances.2021004619.
PubMed 34581757
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label, Dose Escalation/Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and/or High-Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 Gene Rearrangements
- ClinicalTrials.gov ID
- NCT03255096
- Acronym / sponsor ID
- NP39461
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 28 Aug 2017 (actual)
- Primary completion
- 3 Jul 2019 (actual)
- Study completion
- 3 Jul 2019 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Phase (Part 1) | Experimental | Drug: RO6870810, Drug: Venetoclax, Drug: RituximabParticipants will receive either RO6870810 and venetoclax or RO6870810 and venetoclax along with rituximab until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. |
| Expansion Phase (Part 2) | Experimental | Drug: RO6870810, Drug: Venetoclax, Drug: RituximabParticipants will receive RO6870810 and venetoclax along with rituximab (or RO6870810 and venetoclax, if the combination of the 3 drugs is not tolerable) at a recommended dose established in dose escalation phase until disease progression, unacceptable toxicities or withdrawal from treatment for other reasons, or death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Life expectancy >3 months as per investigator's assessment.
- Part 1 and Part 2 Group 1: Participantts with diffuse large B-cell lymphoma (DLBCL) relapsed or refractory to ≥ 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for autologous stem cell transplantation (ASCT) (including due to chemorefractory disease). Participants with transformed FL are eligible, provided DLBCL or HGBL-DH/TH histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. The Sponsor retains the option to limit the number of participants enrolled with transformed FL.
- Part 2, Group 2: Patients identified with DE-DLBCL (expression MYC ≥40%, BCL2 > 50%) and or HGBL-DH/TH, relapsed or refractory to >= 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for ASCT (including due to chemorefractory disease). Patients with transformed follicular lymphoma (FL) are eligible, provided DE-DLBCL and/or HGBL-DH/TH histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. The Sponsor retains the option to limit the number of participants enrolled with transformed FL.
- Part 1 and Part 2: Willing to provide the protocol specified tumor biopsy(ies): at screening a fresh biopsy (if no archival biopsy tissue of less than 3 months prior to treatment and without intercurrent treatment is available); Part 2: Willing to provide an additional biopsy on Cycle 2 Day 15 (+ 2 days).
Key exclusion criteria (33 listed)
- Current central nervous system (CNS) lymphoma or leptomeningeal infiltration.
- New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, within the past 6 months, unstable arrhythmia, or known pericardial disease.
- Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome.
- Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator would preclude safe participation in the study.
- Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
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 |
|---|---|---|
| RO6870810RO6870810 subcutaneously (SC) at dose of 0.30, 0.45, or 0.65 milligram per kilogram (mg/kg) on Days 1-14 of 21-day cycles. | Drug | Dose Escalation Phase (Part 1), Expansion Phase (Part 2) |
| VenetoclaxVenetoclax tablets orally at dose of 400 mg once daily (QD) continuously for 21 days. | Drug | Dose Escalation Phase (Part 1), Expansion Phase (Part 2) |
| RituximabRituximab intravenously (IV) at dose of 375 mg/m^2 weekly during the first 21-day cycle (C1) and on day 1 of each cycle thereafter. | Drug | Dose Escalation Phase (Part 1), Expansion Phase (Part 2) |
Primary outcome
Percentage of Participants With Dose-Limiting Toxiciities (DLT)- Part 1
Time frame: Cycle (C) 1 (21 days)
DLT is defined as any of the toxicities- occurs within the first cycle for which the participant receives the full intended combination doses and number of administrations; is considered to be related to study treatment by the investigator; is not attributed to disease progression or another clearly identifiable cause.
Percentage of Participants With Adverse Events (AEs) - Part 1
Time frame: Up to 36 months
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 1
Time frame: Up to 36 months
Complete Response (CR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- Recommended Dose (RD) Expansion - Part 2
Time frame: Up to 36 months
Overall Response (OR) Rate as Determined by Independent Radiological Central Review (ICR) Using Modified Lugano Response Criteria- RD Expansion - Part 2
Time frame: Up to 36 months
19 secondary outcomes
Percentage of Participants With Adverse Events (AEs) - Part 2
Time frame: Up to 36 months
Percentage of Participants With Clinically Significant Changes in Vital Signs, Physical Examination, Clinical Laboratory Results and Electrocardiogram (ECG) Findings- Part 2
Time frame: Up to 36 months
Maximum Concentration (Cmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Trough Serum Concentration (Cmin) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Cycle 2 and all other subsequent even Cycles (Up to 36 months)
Time of Maximum Concentration (tmax) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Clearance (CL) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Volume of Distribution (Vd) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Area Under the Curve (AUC) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Complete Response (CR) Rate as Determined by the Investigator Based on the Modified Lugano Response Criteria- Part 1 and Part 2
Time frame: Up to 36 months
Complete Response (CR) Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2
Time frame: Up to 36 months
Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of Modified Lugano Response Criteria- Part 1 and Part 2
Time frame: Up to 36 months
Objective Response Rate, as Determined by the ICR and by the Investigator on the Basis of CT Scans Alone- Part 1 and Part 2
Time frame: Up to 36 months
Duration of Response (DoR)- Part 1 and Part 2
Time frame: Up to 36 months
Progression-Free Survival (PFS)- Part 1 and Part 2
Time frame: Up to 36 months
Event-Free Survival (EFS)- Part 1 and Part 2
Time frame: Up to 36 months
Disease-Free Survival (DFS)- Part 1 and Part 2
Time frame: Up to 36 months
Overall Survival (OS)- Part 1 and Part 2
Time frame: Up to 36 months
Half-Life (t1/2) of RO6870810 and its Potential Metabolites- Part 1 and Part 2
Time frame: Pre-dose Day 1,8,15; 0.25,0.5,1,2,4,6,8 hour (h) post-dose Day 1, 15; Day 2 C1; Pre-dose Day 1,8,15; 0.25h post-dose Day 1,8 C2; Pre-dose Day 1,15 C4; 0.25h post-dose Day 1 C4; Pre-dose, 0.25h post-dose Day 1 of subsequent even Cycles (Up to 36 months)
Percentage of Ant-Drug Antibodies (ADA) Against Rituximab - Part 1 and Part 2
Time frame: Pre-dose, End of Infusion Day 1 Cycle 1; Pre-dose Day 1 Cycle 2, 3, 4 , 6 and all other even Cycles (Up to 36 months)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2022.
- Derived from this study: PubMed 34581757Dickinson M, Briones J, Herrera AF, Gonzalez-Barca E, Ghosh N, Cordoba R, Rutherford SC, Bournazou E, Labriola-Tompkins E, Franjkovic I, Chesne E, Brouwer-Visser J, Lechner K, Brennan B, Nuesch E, DeMario M, Ruttinger D, Kornacker M, Hutchings M. Phase 1b study of the BET protein inhibitor RO6870810 with venetoclax and rituximab in patients with diffuse large B-cell lymphoma. Blood Adv. 2021 Nov 23;5(22):4762-4770. doi: 10.1182/bloodadvances.2021004619.
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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 chair
Hoffmann-La Roche
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO6870810, Venetoclax and Rituximab in people with Diffuse Large B-cell Lymphoma and High-Grade B-cell Lymphoma, run by Hoffmann-La Roche at 9 sites in 4 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 21 inclusion and 33 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 24 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Spain, Australia, Denmark. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Dose-Limiting Toxiciities (DLT)- Part 1 (time frame: Cycle (C) 1 (21 days)). The study lists 5 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 NCT03255096, which also lists 1 linked publication.
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 24 Jan 2022.