Non-Hodgkin's LymphomaPhase 1/2NCT00400764

A Study of Dulanermin in Combination With Rituximab in Subjects With Follicular and Other Low Grade, CD20+, Non-Hodgkin's Lymphomas

A Phase 1/2 study testing Dulanermin and Rituximab in people with Non-Hodgkin's Lymphoma, run by Genentech, Inc..

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-Hodgkin's Lymphoma
What is being tested?: Dulanermin and Rituximab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 72 participants
Where: No sites listed yet
Study dates: Jun 2006to May 2010
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

Signed Informed Consent Form
Age ≥ 18 years
History of histologically confirmed CD20+ follicular NHL Grade 1, 2, or 3a
Progression of disease following the most recent treatment with rituximab-containing therapy that resulted in stable disease or a partial or complete response lasting ≥ 6 months
Measurable disease
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., contraceptive pill, intrauterine device [IUD], physical barrier throughout the trial and for 1 year following their final exposure to study treatment).
Life expectancy of > 3 months

Who cannot join

Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure response unless that lesion shows unequivocal progression at baseline
Radiation therapy to a peripheral lesion within 14 days prior to Day 1; Radiation therapy to a thoracic, abdominal, or pelvic field within 28 days prior to Day 1
Chemotherapy, hormonal therapy, radiotherapy, or immunotherapy within 4 weeks prior to Day 1
Patients who have received radioimmunotherapy for relapsed or refractory, follicular NHL are eligible for the study if they received this therapy at least 1 year prior to Day 1, they have adequate bone marrow function, and they have no evidence of myelodysplastic syndrome on bone marrow aspirate/biopsy
Prior treatment with dulanermin or an agonist antibody to DR4 or DR5
Concurrent systemic corticosteroid therapy

Show all 18Show fewer

Evidence of clinically detectable ascites on Day 1
Other invasive malignancies within 5 years prior to Day 1
History or evidence upon physical examination of central nervous system (CNS) disease within 1 year prior to study entry
Active infection requiring parenteral antibiotics on Day 1
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study and fine needle aspirations within 7 days prior to Day 1
Pregnancy or lactation
Serious nonhealing wound, ulcer, or bone fracture
Current or recent participation in another experimental drug study
Clinically significant cardiovascular disease
Known positive test result for HIV, hepatitis B surface antigen (sAg), hepatitis B IgG or IgM core antibody, or hepatitis C antibody
Known sensitivity to murine or human antibodies
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications

About this study

Official title: A Phase Ib/II, Open-Label, Multicenter Study of the Safety, Pharmacokinetics, and Efficacy of Dulanermin Administered Intravenously in Combination With Rituximab to Subjects With Follicular and Other Low-Grade, CD20+, B-Cell Non-Hodgkin's Lymphomas That Have Progressed Following Previous Rituximab Therapy

This Phase Ib/II, open-label, multicenter trial is designed to evaluate the safety, pharmacokinetics, and efficacy of dulanermin when combined with rituximab in subjects with follicular, CD20+, B-cell Non-Hodgkin's Lymphoma (NHL) that has progressed following a response of ≥ 6 months duration to a prior rituximab-containing therapy. The multicenter, international, randomized Phase II part of this study will commence only after the safety and available pharmacokinetic data from the Phase Ib part of the study have been evaluated by the Sponsor and have been provided to participating investigators and the FDA.

Conditions: Non-Hodgkin's Lymphoma
Being tested: Dulanermin, Rituximab
Keywords: NHL, Follicular NHL, Rituxan, Apo2L/TRAIL
Medical subject headings: Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DulanerminDrug
Dulanermin was administered by intravenous (IV) infusion over 1 hour on days 1-5 of each 21-day cycle.
RituximabDrug
Rituximab was administered by intravenous (IV) infusion at 375 mg/m^2 weekly for up to eight doses.

Study groups in NCT00400764
Study group	Role	What they receive
Phase Ib: Dulanermin 4 mg/kg	Experimental	Participants received 4.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Participants also received rituximab administered by IV infusion at 375 mg/m^2 weekly for up to eight doses. Receives: Drug: Dulanermin; Drug: Rituximab
Phase Ib: Dulanermin 8 mg/kg	Experimental	Participants received 8.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Participants also received rituximab administered by IV infusion at 375 mg/m^2 weekly for up to eight doses. Receives: Drug: Dulanermin; Drug: Rituximab
Phase II: Rituximab	Active comparator	Participants received rituximab administered by intravenous (IV) infusion at 375 mg/m^2 weekly for up to eight doses. Receives: Drug: Rituximab
Phase II: Combination Therapy	Experimental	Participants received 8.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Participants also received rituximab administered by IV infusion at 375 mg/m^2 weekly for up to eight doses. Receives: Drug: Dulanermin; Drug: Rituximab
Phase II: Dulanermin	Experimental	Participants received 8.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Receives: Drug: Dulanermin

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase Ib: Number of Participants With a Dose-limiting Toxicity
A dose-limiting toxicity (DLT) was defined as a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 Grade ≥ 3 hematologic or major organ toxicity that was related to study drug (i.e., dulanermin). Although a patient may have experienced a DLT at any time during the study, only events that occurred within the DLT assessment window were considered for dose-escalation decisions and determination of the maximum tolerated dose (MTD).
Measured: The DLT assessment window was defined as the duration required to complete two full cycles of treatment with dulanermin (2 * 21 days) and four doses of rituximab (usually through Day 28).
Number of Participants With Treatment-Emergent Adverse Events by Severity Grade
Safety was assessed through summaries of treatment-emergent adverse events (AEs); AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0, according to the following guidelines: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (Life-threatening or disabling) and Grade 5 (Death related to AE).
Measured: From Baseline through Study Termination (up to a maximum of approximately 13 months for phase Ib and up to approximately 33 months for phase II)
Phase II: Objective Response as Assessed by the Independent Review Facility (IRF)
Objective response was defined as a confirmed or unconfirmed complete response (CR, CRu) or partial response (PR) assessed on the basis of clinical, radiographic (computed tomography (CT) scans of the neck, chest, abdomen, pelvis and inguinal region), and pathologic (i.e., bone marrow) criteria and according to the modified International Working Group (IWG) criteria. All radiographic and clinical data for the evaluation of objective response were submitted to an IRF for blinded and impartial assessment.
Patients without a post-baseline tumor assessment were considered non-responders.
Measured: From Baseline through Study Termination (up to approximately 33 months)
Vital Signs: Change From Baseline in Diastolic and Systolic Blood Pressure at Treatment Termination Visit
Blood pressure was measured at baseline and throughout the study. Change from baseline was calculated using the patient's last recorded measurement at the completion of treatment visit - baseline measurement.
Measured: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
Vital Signs: Change From Baseline in Heart Rate at Treatment Termination Visit
Heart rate was measured at baseline and throughout the study. Change from baseline was calculated using the patient's last recorded measurement at the completion of treatment visit - baseline measurement.
Measured: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
Vital Signs: Change From Baseline in Body Temperature at Treatment Termination Visit
Body temperature was measured at baseline and throughout the study. Change from baseline was calculated using the patients last recorded measurement at the completion of treatment visit - baseline measurement.
Measured: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
Number of Participants With a Clinically Significant Laboratory Abnormality
Laboratory Parameters were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). A clinically significant abnormality was defined as a Grade 3 (severe) or Grade 4 (very severe, life threatening, or disabling) laboratory toxicity according to the NCI CTCAE v3.0.
Measured: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms).
Mean Serum Concentration of Dulanermin
The dulanermin serum concentration was measured using enzyme linked immunosorbent assay (ELISA).
Measured: Blood samples were taken 0.5, 1.5, 2, 3, 5, 7 and 24 hours after the start of the infusion on Day 1 of Cycle 1.

Secondary outcomes (4)

Phase II: Progression Free Survival
Progression free survival (PFS) was defined as the time from randomization to documented disease progression or death, whichever occurred first and was based on the investigator's assessment using the modified IWG criteria. Kaplan-Meier methods were used to estimate median time to PFS. Data for patients without disease progression or death on study were censored at the time of the last tumor assessment.
Measured: From Baseline through Study Termination (up to approximately 33 months)
Phase II: Overall Survival
Median overall survival could not be estimated because of the low number of deaths at the time of study termination.
Measured: From Baseline through Study Termination (up to approximately 33 months)
Phase II: Objective Response as Assessed by the Investigator
Objective response was defined as a confirmed or unconfirmed complete response(CR, CRu) or partial response (PR) assessed on the basis of clinical, radiographic (computed tomography (CT) scans of the neck, chest, abdomen, pelvis and inguinal region), and pathologic (i.e., bone marrow) criteria and according to the modified International Working Group (IWG) criteria. Patients without a post-baseline tumor assessment were considered non-responders.
Measured: From Baseline through Study Termination (up to approximately 33 months)
Phase II: Duration of Response as Assessed by the Investigator
An event was defined as documented disease progression or death on study, whichever occurred first. Duration of objective response was defined only for patients with an objective response as determined by the investigator and was the time from the initial response to disease progression or death on study.
Kaplan-Meier methods were used to estimate median, percentiles, and range of duration of response.
Measured: From Baseline through Study Termination (up to approximately 33 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2006May 2010

First posted17 Nov 2006 (estimated)
Study startJun 2006
Primary completionMay 2010

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 (1)Papers the sponsor has linked to this study.
Other trials for Non-Hodgkin's 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: Single group
Masking: None (open label)
Enrolment: 72 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00400764
Sponsor's protocol ID: APO3585g
Status last verified: Nov 2011
First submitted: 15 Nov 2006
Last updated: 23 Nov 2011
Results posted: Yes, on ClinicalTrials.gov

Publications

Cheah CY, Belada D, Fanale MA, Janikova A, Czucman MS, Flinn IW, Kapp AV, Ashkenazi A, Kelley S, Bray GL, Holden S, Seymour JF. Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study. Lancet Haematol. 2015 Apr;2(4):e166-74. doi: 10.1016/S2352-3026(15)00026-5. Epub 2015 Mar 25.
PubMed 26687959

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma

All Non-Hodgkin's Lymphoma trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib/II, Open-Label, Multicenter Study of the Safety, Pharmacokinetics, and Efficacy of Dulanermin Administered Intravenously in Combination With Rituximab to Subjects With Follicular and Other Low-Grade, CD20+, B-Cell Non-Hodgkin's Lymphomas That Have Progressed Following Previous Rituximab Therapy
ClinicalTrials.gov ID: NCT00400764
Acronym / sponsor ID: APO3585g
Conditions: Non-Hodgkin's Lymphoma
Keywords: NHL, Follicular NHL, Rituxan, Apo2L/TRAIL
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 72 participants (actual)
Lead sponsor: Genentech, Inc.Industry (pharma, biotech, devices)
Collaborators: Amgen
Study start: Jun 2006
Primary completion: May 2010 (actual)
First posted: 17 Nov 2006 (estimated)
Results: Posted 7 Oct 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Phase Ib: Dulanermin 4 mg/kg	Experimental	Drug: Dulanermin, Drug: RituximabParticipants received 4.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Participants also received rituximab administered by IV infusion at 375 mg/m^2 weekly for up to eight doses.
Phase Ib: Dulanermin 8 mg/kg	Experimental	Drug: Dulanermin, Drug: RituximabParticipants received 8.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Participants also received rituximab administered by IV infusion at 375 mg/m^2 weekly for up to eight doses.
Phase II: Rituximab	Active comparator	Drug: RituximabParticipants received rituximab administered by intravenous (IV) infusion at 375 mg/m^2 weekly for up to eight doses.
Phase II: Combination Therapy	Experimental	Drug: Dulanermin, Drug: RituximabParticipants received 8.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles. Participants also received rituximab administered by IV infusion at 375 mg/m^2 weekly for up to eight doses.
Phase II: Dulanermin	Experimental	Drug: DulanerminParticipants received 8.0 mg/kg/day dose of dulanermin, administered by intravenous (IV) infusion for 5 consecutive days at the start of each 21-day treatment cycle for up to four cycles.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Signed Informed Consent Form
Age ≥ 18 years
History of histologically confirmed CD20+ follicular NHL Grade 1, 2, or 3a
Progression of disease following the most recent treatment with rituximab-containing therapy that resulted in stable disease or a partial or complete response lasting ≥ 6 months
Measurable disease

Key exclusion criteria (18 listed)

Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure response unless that lesion shows unequivocal progression at baseline
Radiation therapy to a peripheral lesion within 14 days prior to Day 1; Radiation therapy to a thoracic, abdominal, or pelvic field within 28 days prior to Day 1
Chemotherapy, hormonal therapy, radiotherapy, or immunotherapy within 4 weeks prior to Day 1
Patients who have received radioimmunotherapy for relapsed or refractory, follicular NHL are eligible for the study if they received this therapy at least 1 year prior to Day 1, they have adequate bone marrow function, and they have no evidence of myelodysplastic syndrome on bone marrow aspirate/biopsy
Prior treatment with dulanermin or an agonist antibody to DR4 or DR5

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
DulanerminDulanermin was administered by intravenous (IV) infusion over 1 hour on days 1-5 of each 21-day cycle.	Drug	Phase II: Combination Therapy, Phase II: Dulanermin, Phase Ib: Dulanermin 4 mg/kg, Phase Ib: Dulanermin 8 mg/kg
RituximabRituximab was administered by intravenous (IV) infusion at 375 mg/m^2 weekly for up to eight doses.	Drug	Phase II: Combination Therapy, Phase II: Rituximab, Phase Ib: Dulanermin 4 mg/kg, Phase Ib: Dulanermin 8 mg/kg

Primary outcome

Phase Ib: Number of Participants With a Dose-limiting Toxicity
Time frame: The DLT assessment window was defined as the duration required to complete two full cycles of treatment with dulanermin (2 * 21 days) and four doses of rituximab (usually through Day 28).
A dose-limiting toxicity (DLT) was defined as a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 Grade ≥ 3 hematologic or major organ toxicity that was related to study drug (i.e., dulanermin). Although a patient may have experienced a DLT at any time during the study, only events that occurred within the DLT assessment window were considered for dose-escalation decisions and determination of the maximum tolerated dose (MTD).
Number of Participants With Treatment-Emergent Adverse Events by Severity Grade
Time frame: From Baseline through Study Termination (up to a maximum of approximately 13 months for phase Ib and up to approximately 33 months for phase II)
Safety was assessed through summaries of treatment-emergent adverse events (AEs); AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0, according to the following guidelines: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (Life-threatening or disabling) and Grade 5 (Death related to AE).
Phase II: Objective Response as Assessed by the Independent Review Facility (IRF)
Time frame: From Baseline through Study Termination (up to approximately 33 months)
Objective response was defined as a confirmed or unconfirmed complete response (CR, CRu) or partial response (PR) assessed on the basis of clinical, radiographic (computed tomography (CT) scans of the neck, chest, abdomen, pelvis and inguinal region), and pathologic (i.e., bone marrow) criteria and according to the modified International Working Group (IWG) criteria. All radiographic and clinical data for the evaluation of objective response were submitted to an IRF for blinded and impartial assessment. Patients without a post-baseline tumor assessment were considered non-responders.
Vital Signs: Change From Baseline in Diastolic and Systolic Blood Pressure at Treatment Termination Visit
Time frame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
Blood pressure was measured at baseline and throughout the study. Change from baseline was calculated using the patient's last recorded measurement at the completion of treatment visit - baseline measurement.
Vital Signs: Change From Baseline in Heart Rate at Treatment Termination Visit
Time frame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
Heart rate was measured at baseline and throughout the study. Change from baseline was calculated using the patient's last recorded measurement at the completion of treatment visit - baseline measurement.
Vital Signs: Change From Baseline in Body Temperature at Treatment Termination Visit
Time frame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
Body temperature was measured at baseline and throughout the study. Change from baseline was calculated using the patients last recorded measurement at the completion of treatment visit - baseline measurement.
Number of Participants With a Clinically Significant Laboratory Abnormality
Time frame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms).
Laboratory Parameters were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). A clinically significant abnormality was defined as a Grade 3 (severe) or Grade 4 (very severe, life threatening, or disabling) laboratory toxicity according to the NCI CTCAE v3.0.
Mean Serum Concentration of Dulanermin
Time frame: Blood samples were taken 0.5, 1.5, 2, 3, 5, 7 and 24 hours after the start of the infusion on Day 1 of Cycle 1.
The dulanermin serum concentration was measured using enzyme linked immunosorbent assay (ELISA).

4 secondary outcomes

Phase II: Progression Free Survival
Time frame: From Baseline through Study Termination (up to approximately 33 months)
Phase II: Overall Survival
Time frame: From Baseline through Study Termination (up to approximately 33 months)
Phase II: Objective Response as Assessed by the Investigator
Time frame: From Baseline through Study Termination (up to approximately 33 months)
Phase II: Duration of Response as Assessed by the Investigator
Time frame: From Baseline through Study Termination (up to approximately 33 months)

Results and safety

Results posted to the registry on 7 Oct 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase Ib - Dulanermin 4 mg/kg	6	0
Phase Ib - Dulanermin 8 mg/kg	6	2
Phase II - Rituximab	0	0
Phase II - Combination Therapy	0	0
Phase II - Dulanermin	0	0

Primary outcome: Phase Ib: Number of Participants With a Dose-limiting Toxicity

Time frame: The DLT assessment window was defined as the duration required to complete two full cycles of treatment with dulanermin (2 * 21 days) and four doses of rituximab (usually through Day 28).. Number. Unit: participants

Measure	Phase Ib - Dulanermin 4 mg/kg n = 6	Phase Ib - Dulanermin 8 mg/kg n = 6
Value	0	0

Population analysed: The DLT-evaluable population consisted of all patients enrolled in the Phase Ib who received at least two complete cycles of dulanermin and four doses of rituximab and complete study assessments through the DLT Assessment Window without a DLT (usually through Day 28) or experienced a DLT and withdrew from the study within the DLT Assessment Window.

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events by Severity Grade

Time frame: From Baseline through Study Termination (up to a maximum of approximately 13 months for phase Ib and up to approximately 33 months for phase II). Number. Unit: participants

Measure	Phase Ib - Dulanermin 4 mg/kg n = 6	Phase Ib - Dulanermin 8 mg/kg n = 6	Phase II - Rituximab n = 22	Phase II - Combination Therapy n = 26	Phase II - Dulanermin n = 11
Grade 5 AE	0	0	1	0	0
Grade 4 AE	1	0	0	0	0
Grade 3 AE	1	3	1	6	0
Grade 2 AE	4	1	8	10	4
Grade 1 AE	0	2	6	7	4
Any Grade AEs	6	6	16	23	8

Population analysed: Safety Evaluable population, consisting of all randomized patients who received at least one dose of treatment.

Primary outcome: Phase II: Objective Response as Assessed by the Independent Review Facility (IRF)

Time frame: From Baseline through Study Termination (up to approximately 33 months). Number. Unit: participants

Measure	Rituximab n = 22	Combination Therapy n = 25	Dulanermin n = 11
Total Objective Response	14	16	1
Complete Response	5	3	0
Complete Response unconfirmed	0	2	0
Partial Response	9	11	1

Population analysed: The phase II Efficacy-Evaluable population consisted of all randomized patients who received at least one dose of study treatment and had measurable disease at baseline, as assessed by the IRF.

Primary outcome: Vital Signs: Change From Baseline in Diastolic and Systolic Blood Pressure at Treatment Termination Visit

Time frame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms). Mean (Standard Deviation). Unit: mmHg

Measure	Phase Ib - Dulanermin 4 mg/kg n = 6	Phase Ib - Dulanermin 8 mg/kg n = 6	Phase II - Rituximab n = 22	Phase II - Combination Therapy n = 26	Phase II - Dulanermin n = 11
Diastolic Blood Pressure	-8.7 (10.9)	-5.2 (7.9)	2.3 (9.9)	1.6 (9.2)	-0.8 (5.6)
Systolic Blood Pressure	-3.2 (16.8)	-4.7 (10.9)	-3.4 (14.8)	-2.2 (19.6)	-4.2 (9.5)

Population analysed: Safety Evaluable population, consisting of all randomized patients who received at least one dose of treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events occurring on or after the first treatment through Study Termination (up to approximately 13 months for phase Ib and up to approximately 33 months for phase II) are summarized.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase Ib - Dulanermin 4 mg/kg	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
Phase Ib - Dulanermin 8 mg/kg	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
Phase II - Rituximab	1 of 22 (4.5%)	16 of 22 (72.7%)	Not reported
Phase II - Combination Therapy	4 of 26 (15.4%)	22 of 26 (84.6%)	Not reported
Phase II - Dulanermin	0 of 11 (0%)	8 of 11 (72.7%)	Not reported

Limitations and caveats (from the sponsor): The Sponsor terminated the study on 5 May 2010, prior to the completion of the 36-month follow-up (FU) period, based on the primary analysis results. All patients were off-study or in survival FU (the treatment period was completed).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26687959Cheah CY, Belada D, Fanale MA, Janikova A, Czucman MS, Flinn IW, Kapp AV, Ashkenazi A, Kelley S, Bray GL, Holden S, Seymour JF. Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study. Lancet Haematol. 2015 Apr;2(4):e166-74. doi: 10.1016/S2352-3026(15)00026-5. Epub 2015 Mar 25.

Related trials for Non-Hodgkin's Lymphoma

RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Active, not recruitingPhase 2
A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy
B Cell ALL, B-Cell Lymphoma
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma

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.

Chia Portera, PhD., M.D study director

Genentech, Inc.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dulanermin and Rituximab in people with Non-Hodgkin's Lymphoma, run by Genentech, Inc..

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 8 inclusion and 18 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: stopped early, as of the sponsor's last update on 23 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.

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 7 Oct 2011). 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?

Phase Ib: Number of Participants With a Dose-limiting Toxicity (time frame: The DLT assessment window was defined as the duration required to complete two full cycles of treatment with dulanermin (2 * 21 days) and four doses of rituximab (usually through Day 28).). The study lists 8 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 NCT00400764, 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 23 Nov 2011.