Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments ibrutinib, placebo, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or equivalent)
Phase phase 3
Targets BTK, CD20
Sponsor Janssen Research & Development, LLC
Collaborator Pharmacyclics LLC.
Start date September 2013
End date June 2018
Trial size 843 participants
Trial identifier NCT01855750, 2013-000959-40, CR102118, PCI-32765DBL3001, U1111-1139-6222

Summary

The purpose of this study is to evaluate if ibrutinib administered in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the clinical outcome in newly diagnosed patients with non-germinal center B-cell subtype (GCB) of diffuse large B-cell lymphoma (DLBCL).

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, caregiver, investigator)
Primary purpose treatment
Arm
(Placebo Comparator)
Treatment Arm A = placebo + R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone)
placebo
4 matched capsules administered by mouth once daily (21-day cycles)
rituximab
375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
doxorubicin
50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
vincristine
1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
prednisone (or equivalent)
100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle
(Experimental)
Treatment Arm B = ibrutinib + R-CHOP
ibrutinib
560 mg capsules administered by mouth once daily (21-day cycles)
rituximab
375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
doxorubicin
50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
vincristine
1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)
prednisone (or equivalent)
100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle

Primary Outcomes

Measure
Event-free survival
time frame: Up to disease progression, relapse from complete response, initiation of subsequent systemic antilymphoma therapy after completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first, up to Year 7

Secondary Outcomes

Measure
Progression-free survival
time frame: Up to disease progression, relapse from complete response, or death, whichever occurs first, up to Year 7
Overall survival
time frame: Up to the date of the participants death, up to Year 7
Complete response rate
time frame: Up to completion of chemotherapy treatment, up to Year 7
Time to worsening symptoms in the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)
time frame: Up to the start date of the worsening of patient symptoms, up to Year 7
Oral plasma clearance of ibrutinib
time frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
Oral volume of distribution at steady state of ibrutinib
time frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
Area under the plasma concentration-time curve of ibrutinib
time frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
Minimum observed plasma concentration of ibrutinib
time frame: Predose Day 1 of Cycles 1, 2, and 3, and postdose 1 h, 2 h, and 4 h of Cycles 1 and 2
Number of participants affected by an adverse event
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: - No prior treatment for diffuse B-cell lymphoma (DLBCL) - Histologically-confirmed non-germinal center B-cell subtype DLBCL - Stage II (not candidates for local x-ray therapy), III, or IV disease by the Ann Arbor Classification - At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma - Revised International Prognostic Index score of >=1 - Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2 - Hematology and biochemical laboratory values within protocol-defined parameters prior to random assignment and at baseline - Left ventricular ejection fraction within institutional normal limits, as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan - Agrees to protocol-defined use of effective contraception (for women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose of study drug, whichever is later; for men, these restrictions apply for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later) - Men must agree to not donate sperm during and after the study for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later - Women of childbearing potential must have a negative serum or urine pregnancy test at screening Exclusion Criteria: - Major surgery within 4 weeks of random assignment - Known central nervous system or primary mediastinal lymphoma - Prior history of indolent lymphoma - Diagnosed or treated for malignancy other than DLBCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease - History of stroke or intracranial hemorrhage within 6 months prior to random assignment - Requires anticoagulation with warfarin or equivalent vitamin K antagonists - Requires treatment with strong CYP3A inhibitors - Prior anthracycline use >=150 mg/m2 - Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification - Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics - Women who are pregnant or breastfeeding - Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk

Additional Information

Official title A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed Non-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
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 to compare the efficacy and safety of ibrutinib in combination with R-CHOP versus R-CHOP alone in adult patients newly diagnosed non-GCB DLBCL. The study will include screening, active treatment, and posttreatment follow-up phases. The study will end when 50% of participants have died or the sponsor terminates the study, whichever occurs first (up to approximately 7 years). Approximately 800 participants will be randomly assigned in a 1:1 ratio to receive either placebo+R-CHOP (treatment arm A) or ibrutinib+R-CHOP (treatment arm B). All participants will receive R-CHOP as background therapy for 6 or 8 cycles (21 days per cycle) prespecified according to local practice. After 4 treatment cycles, an interim response assessment will be performed to evaluate disease progression for each participant. Participants with progressive disease or relapsed disease after complete response will be discontinued from treatment. Participants who discontinue R-CHOP without disease progression will continue study drug (placebo or ibrutinib) until 6 or 8 cycles are completed, disease progression, or unacceptable toxicity, whichever occurs first. After completion of study drug, participants will undergo assessment of tumor response based on the Revised Response Criteria for Malignant Lymphoma. Participants with documented residual disease upon completion of at least 6 cycles of R-CHOP therapy are considered eligible to initiate subsequent antilymphoma therapy. Serial pharmacokinetic samples will be collected before and after dosing, and safety will be monitored throughout the study.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Janssen Research & Development, LLC.