Clinical trial NCT00400764: A Study of Dulanermin in Combination With Rituximab in Subjects With Follicular and Other Low Grade, CD20+, Non-Hodgkin's Lymphomas
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin's Lymphoma
Keywords: NHL
Follicular NHL
Rituxan
Apo2L/TRAIL
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2006-11-17
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Phase Ib: Number of Participants With a Dose-limiting Toxicity
timeFrame: 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).
measure: Number of Participants With Treatment-Emergent Adverse Events by Severity Grade
timeFrame: 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)
measure: Phase II: Objective Response as Assessed by the Independent Review Facility (IRF)
timeFrame: From Baseline through Study Termination (up to approximately 33 months)
measure: Vital Signs: Change From Baseline in Diastolic and Systolic Blood Pressure at Treatment Termination Visit
timeFrame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
measure: Vital Signs: Change From Baseline in Heart Rate at Treatment Termination Visit
timeFrame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
measure: Vital Signs: Change From Baseline in Body Temperature at Treatment Termination Visit
timeFrame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms)
measure: Number of Participants With a Clinically Significant Laboratory Abnormality
timeFrame: Baseline and Treatment Termination visit (8 weeks for Rituximab arm and 12 weeks for combination and Dulanermin arms).
measure: Mean Serum Concentration of Dulanermin
timeFrame: 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:
measure: Phase II: Progression Free Survival
timeFrame: From Baseline through Study Termination (up to approximately 33 months)
measure: Phase II: Overall Survival
timeFrame: From Baseline through Study Termination (up to approximately 33 months)
measure: Phase II: Objective Response as Assessed by the Investigator
timeFrame: From Baseline through Study Termination (up to approximately 33 months)
measure: Phase II: Duration of Response as Assessed by the Investigator
timeFrame: From Baseline through Study Termination (up to approximately 33 months)
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Chia Portera, PhD., M.D
role: STUDY_DIRECTOR
References:
citation: 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.