ViPOR Combination

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

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

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.

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.

Live record on ClinicalTrials.gov →

• Patients must have histologically or cytologically confirmed B-cell lymphoma confirmed by the Laboratory of Pathology, NCI, as follows:
• 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).
• 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 CNS lymphoma are not eligible.
• Relapsed and/or refractory DLBCL and subtypes, including transformed lymphoma as well as High grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s).

Inclusion criteria as written on the registry, trimmed. The full list, with exclusions, is on the live record.