Phase 1b/2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
National Cancer Institute (NCI)
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....
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…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Patients must have histologically or cytologically confirmed B-cell lymphoma confirmed by the Laboratory of Pathology, NCI, as follows: Phase1b * Aggressive B-cell lymphoma: includes DLBCL and subtypes, transformed lymphoma, Burkitt lymphoma, as well as High-grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s). -Indolent B-cell lymphoma: * CLL/SLL is excluded given alternative dosing of FDA-approved venetoclax for relapsed 17p CLL and increased risk of TLS with CLL/SLL compared to other non-Hodgkin lymphomas. * NOTE: Patients with known active…
Interventions
- DrugVenetoclax
Administered orally, days 2-14, at varying doses of 200-800 mg (based upon assigned dose level); every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
- DrugIbrutinib
Administered orally, days 1-14, at a dose of 560 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
- DrugPrednisone
Administered orally, days 1-7, at a dose of 100 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
- BiologicalObinutuzumab
Administered intravenously, days 1 and 2, at a dose of 1000 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
- DrugRevlimid (lenalidomide)
Administered orally, days 1-15, at a dose of 15 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
Location
- National Institutes of Health Clinical CenterBethesda, Maryland