Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments bendamustine, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, pci-32765 (ibrutinib), placebo
Phase phase 3
Target CD20
Sponsor Janssen Research & Development, LLC
Collaborator Pharmacyclics
Start date January 2014
End date October 2017
Trial size 403 participants
Trial identifier NCT01974440, 2013-003093-27, CR102786, PCI-32765FLR3001

Summary

The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib) administered in combination with either bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in adult participants with previously treated indolent Non-Hodgkin lymphoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Placebo Comparator)
Treatment Arm A = background immune-chemotherapy (bendamustine and rituximab [BR] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) for 6 cycles + placebo.
bendamustine
90 milligram per meter square (mg/m^2) administered intravenously on Days 1 to 2 of Cycles 1 to 6.
rituximab
375 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.
cyclophosphamide
750 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.
doxorubicin
50 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.
vincristine
1.4 mg/m^2 (maximum total 2 mg) administered intravenously on Day 1 of Cycles 1 to 6.
prednisone
100 mg administered orally on Days 1 to 5 of Cycles 1 to 6.
placebo
Placebo (4 capsules) matched to ibrutinib administered orally once daily, continuously starting on Cycle 1, Day 1.
(Experimental)
Treatment Arm B = background immune-chemotherapy (BR or R-CHOP) for 6 cycles + PCI-32765 (Ibrutinib).
bendamustine
90 milligram per meter square (mg/m^2) administered intravenously on Days 1 to 2 of Cycles 1 to 6.
rituximab
375 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.
cyclophosphamide
750 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.
doxorubicin
50 mg/m^2 administered intravenously on Day 1 of Cycles 1 to 6.
vincristine
1.4 mg/m^2 (maximum total 2 mg) administered intravenously on Day 1 of Cycles 1 to 6.
prednisone
100 mg administered orally on Days 1 to 5 of Cycles 1 to 6.
pci-32765 (ibrutinib)
560 mg (4*140 mg) capsules administered orally once daily, continuously starting on Cycle 1, Day 1.

Primary Outcomes

Measure
Progression-free survival
time frame: Up to approximately 7 years after the first participant is randomized

Secondary Outcomes

Measure
Overall survival
time frame: Up to approximately 7 years after the first participant is randomized
Complete response rate
time frame: Up to approximately 7 years after the first participant is randomized
Overall response rate
time frame: Up to approximately 7 years after the first participant is randomized
Duration of response
time frame: Up to approximately 7 years after the first participant is randomized
Participants with change in patient-reported lymphoma symptoms and concerns as measured by the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
time frame: Up to approximately 7 years after the first participant is randomized
Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
time frame: Up to 30 days after the last dose of study medication

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically confirmed diagnosis of B-cell indolent Non-Hodgkin lymphoma with histological subtype limited to follicular lymphoma or marginal zone lymphoma, at initial diagnosis and without evidence of pathological transformation or clinical signs suggesting transformation - At least 1 prior treatment with a CD20 antibody combination chemo-immunotherapy regimen - Disease that has relapsed or was refractory after prior chemo-immunotherapy - At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma 2007 - Eastern Cooperative Oncology Group performance status grade 0 or 1 - Laboratory values within protocol-defined parameters - Agrees to protocol-defined use of effective contraception - Men must agree not to donate sperm during and after the study for 6 months after the last dose of bendamustine, 12 months after the last dose of rituximab, or 3 months after the last dose of study medication, whichever is later - Women of childbearing potential must have a negative serum or urine pregnancy test at Screening Exclusion Criteria: - Prior treatment according to protocol-defined criteria - Unable to receive background chemotherapy based on prior treatment history and cardiac function - Known central nervous system lymphoma - Diagnosed or treated for malignancy other than indolent Non-Hodgkin lymphoma - History of stroke or intracranial hemorrhage within 6 months prior to randomization - Requires anticoagulation with warfarin or equivalent Vitamin K antagonists - Requires treatment with strong CYP3A inhibitors - Clinically significant cardiovascular disease - Known history of human immunodeficiency virus or active hepatitis C virus (HCV; ribonucleic acid [RNA] polymerase chain reaction [PCR]-positive) or active hepatitis B virus (HBV; DNA PCR-positive) infection or any uncontrolled active systemic infection requiring intravenous antibiotics - Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk - Women who are pregnant or breastfeeding

Additional Information

Official title A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Either Bendamustine and Rituximab (BR) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Previously Treated Indolent Non-Hodgkin Lymphoma (iNHL)
Description This is a randomized (individuals assigned to study treatment by chance), double-blind (individuals and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study in approximately 400 adult participants with follicular lymphoma or marginal zone lymphoma. The study will include the following phases: Screening, Treatment, and a Post-treatment Follow-up. Eligible participants will be randomly assigned in a 1:1 ratio to either treatment Arm A (background immune-chemotherapy + placebo) or treatment Arm B (background immune-chemotherapy + 560 milligram [mg] of ibrutinib). All participants will receive 6 cycles of background immune-chemotherapy with either BR or R-CHOP in combination with either placebo (Arm A) or ibrutinib (Arm B). Selection of background immune-chemotherapy will be based on prior treatment history and cardiac function. After completion of background immune-chemotherapy, study drug (ibrutinib or placebo) will continue until disease progression, unacceptable toxicity, or study end, whichever comes first. Assessment of tumor response and progression will be conducted in accordance with the Revised Response Criteria for Malignant Lymphoma. Serial pharmacokinetic (study of what a drug does to the body) blood samples will be collected. Safety will be assessed throughout the study.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Janssen Research & Development, LLC.