NCT02747732

Study of Ibrutinib in Combination With Bendamustine and Rituximab for Patients With Relapsed/Refractory Aggressive BCL

A Phase II Study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (Ibrutinib), in Combination With Bendamustine and Rituximab (BR) for Patients With Relapsed/Refractory Aggressive B Cell Lymphomas

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: Meirav Kedmi MD · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 2 study of the Bruton's Tyrosine Kinase Inhibitor, PCI-32765 (ibrutinib), in combination with bendamustine and rituximab (BR) in subjects with previously treated aggressive B cell non Hodgkin lymphoma (aB-NHL) including any subtype of diffuse large B cell lymphoma (DLBCL) primary mediastinal B cell lymphoma (PMBCL), double and triple hit DLBCL, transformed indolent lymphoma, unclassifiable aggressive B cell lymphoma between DLBCL and Burkitt lymphoma. Patients with CNS involvement (primary or secondary) will be excluded. Ibrutinib (IMBRUVICA®; PCI-32765; JNJ-54179060) is a first-in-class, potent, orally-administered covalently-binding small molecule inhibitor of Bruton's tyrosine kinase currently FDA approved for the treatment of relapsed Mantle cell lymphoma (MCL), Chronic Lymphocytic Leukemia (CLL) and waldenstrom Macroglobulinemia (WM).It is under constant investigation for the treatment of other B-cell malignancies. The initial approval of ibrutinib was received on 13 November 2013 by the United States Food and Drug Administration for the treatment of adult patients with MCL who have received at least 1 prior therapy. Ibrutinib has not been approved for marketing for the treatment of aggressive B cell lymphoma although Phase I trial in this setting has already been published. In Israel ibrutinib is registered for the treatment of MCL and CLL.

Detailed description

This is a phase II single arm clinical trial that is designed to test the efficacy of ibrutinib in combination with BR in relapsed aB-NHL either as third line post ASCT or as second or third line in non-transplant eligible patients. Patients will be referred for this study from all medical centers in Israel through the Israeli Lymphoma Working Group, but will be treated only in Chaim Sheba Medical center. The study will include a Screening Phase, Treatment Phase, and Post- treatment Follow-up Phase. Subject eligibility will be determined up to 30 days prior to therapy initiation. The treatment Phase will extend from cycle 1 day 1 until study drug discontinuation, either due to progression, toxicity, or due to referral to allo- SCT. Approximately 72 eligible subjects will be stratified by background chemotherapy treatment refractory versus relapsed disease aB-NHL histology, and number of prior lines of therapy. All subject will receive BR protocol and ibrutinib 560mg per day. Ibrutinib will be administered orally once daily starting on cycle 1, day 1, on a continuous schedule until disease progression, referral for allo-SCT, unacceptable toxicity whichever comes first. The post-treatment Follow-up Phase will begin at the end of 6 cycles of BR. Subjects who discontinue for reasons other than disease progression must continue disease evaluations. The Post-treatment Follow-up Phase will continue until death, loss to follow up, consent withdrawal, or study end, whichever occurs first. Assessment of tumor response and progression will be conducted in accordance with the Lugano criteria for Malignant Lymphoma. The investigator will evaluate sites of disease by radiological imaging, physical examination, or other procedures as necessary. The primary efficacy analysis of ORR will be based on investigator assessment. At each site visit, subjects will be evaluated for toxicity. Safety evaluations will include adverse event monitoring, physical examinations, concomitant medication usage, and clinical laboratory parameters.

Conditions

• Diffuse Large B Cell Lymphoma
• Primary Mediastinal (Thymic) Large B-cell Lymphoma
• Transformed Indolent Lymphoma
• Recurrent Disease
• Refractory Cancer

Interventions

Type	Name	Description
DRUG	Bendamustine 90 mg/m2 IV on Days 1-2, Cycles 1-6	Therapy initiation 30 days max from screening. Bendamustine 90 mg/m2 IV on Days 1-2, Cycles 1-6 Rituximab 375 mg/m2 IV Day 1, Cycles 1-6; a cycle is defined as 28 days Ibrutinib, 560 mg orally, once daily, continuously starting on Cycle 1, Day 1 until disease progression, toxicity or referral for allo-SCT

Timeline

• Start date: 2016-12-01
• Primary completion: 2020-06-01
• Completion: 2021-10-01
• First posted: 2016-04-22
• Last updated: 2019-04-23

Locations

2 sites across 1 country: Israel