Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma

Lymphoma Clinical Trial

Official title: Phase 1b/2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma

Status Recruiting

Clinical Trial Summary

Background:

B-cell lymphoma is a cancer of white blood cells found in the lymph nodes. It affects the system that fights infections and disease. Researchers want to learn how certain drugs work together to treat B-cell lymphomas. The drugs are venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR).

Objective:

To study the safety of ViPOR for people with B-cell lymphoma.

Eligibility:

People ages 18 and older with B-cell lymphoma whose cancer has returned or not improved after treatment

Design:

Participants will be screened with:

• Medical history

• Physical exam

• Blood, urine, and heart tests

• Tissue sample from previous procedure

• Imaging scans

• Registration for counseling on the risks of lenalidomide. They must get counseling at least every 28 days.

Participants will have a bone marrow aspiration before treatment.

Participants may have tumor samples taken.

Participants will get ViPOR in 21-day cycles. For up to 6 cycles:

• Participants will get one drug by IV on days 1 and 2.

• Participants will take the other four drugs by mouth on most days. After their first dose of venetoclax, they will stay in the clinic for at least 8 hours and return the next day for monitoring. They may be admitted for more drugs or monitoring.

Participants will keep a drug diary.

Participants will have a physical exam and blood and urine tests at least once per cycle. They will have scans 4 times over 6 cycles.

Participants will have a visit about 1 month after their last dose of study drug. They will then have visits every few months for 3 years, and once a year for years 4 and 5. Visits include a physical exam, blood tests, and scans....

Clinical Trial Description

Background:

Combination chemotherapy with Rituximab has been the mainstay of treatment for CD20-positive B-cell lymphomas

Significant advances have been made in curing aggressive B-cell lymphomas with chemoimmunotherapy but indolent lymphomas and relapsed/refractory aggressive lymphomas remain mostly incurable with chemotherapy alone

Targeted therapies aimed at disrupting key survival pathways in lymphoid malignancies are emerging and showing significant activity in NHL in both the relapsed and first-line settings

Mechanistically-based combinations of targeted agents are likely to benefit patients who cannot tolerate or who relapse after or are refractory to standard chemoimmunotherapy

ViPOR targets major survival pathways in B-cell lymphomas including BCL-2 (apoptosis); BTK (B-cell receptor signaling and NFKB); Cereblon (NFKB) and CD20.

Objectives:

Phase 1b: To determine the maximum tolerated dose (MTD) and the safety and toxicity profile of the combination of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab and Revlimid(R) (ViPOR) in relapsed/refractory B-cell malignancies

Phase 2: To determine the overall response rate (ORR) and complete response (CR) rate of ViPOR in relapsed/refractory B-cell malignancies

Eligibility:

Women and men greater than or equal 18 years of age

ECOG performance status of less than or equal to 2

Histologically or cytologically confirmed relapsed and/or refractory B-cell lymphoma, excluding CLL/SLL. NOTE: untreated and relapsed and/or refractory MCL are included in the phase 2 MCL expansion.

Adequate organ function unless dysfunction secondary to lymphoma effect

Design:

Open-label, single-center, non-randomized phase 1b/2 study

Phase 1b: Standard 3 + 3 design will be used to determine the MTD of dose-escalated venetoclax with fixed dose ibrutinib, prednisone, obinutuzumab and Revlimid(R) (ViPOR) in relapsed/refractory B-cell malignancies

Phase 2: Expansion cohorts of aggressive and indolent non-MCL patients and MCL patients will be treated at the MTD to determine the ORR and CR rate in these subtypes.

Maximum 6 cycles of combination targeted therapy every 21 days

To explore all dose levels in both non-MCL and MCL patient cohorts in the phase 1b study, and to assess the ORR and CR rate in aggressive and indolent non-MCL and MCL patient cohorts in a phase 2 dose expansion at the MTD, the accrual ceiling will be set at 145 patients. ;

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Non-Hodgkin Lymphoma

• NCT number: NCT03223610
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: NCIMO Referral Office
• Phone: (888) 624-1937
• Email: ncimo_referrals@mail.nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 9, 2018
• Completion date: December 1, 2026