Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid in Combination With Polatuzumab (ViPOR-P) in Relapsed/Refractory B-cell Lymphoma
- Conditions
- LymphomaNon-Hodgkin LymphomaDiffuse Large B-Cell LymphomaBurkitt Lymphoma
- Interventions
- Registration Number
- NCT04739813
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Background:
Aggressive B-cell lymphomas can be cured but people with disease that resists treatment or that returns after treatment have poor outcomes with standard therapies. Indolent B-cell lymphomas are generally incurable with standard therapy and treatment is aimed at controlling symptoms and achieving a durable remissions. Researchers want to see if a combination of drugs can help patients with both aggressive and indolent B-cell lymphomas.
Objective:
To learn if it is safe and effective to give polatuzumab along with venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide to people with certain B-cell lymphomas.
Eligibility:
Adults ages 18 and older with relapsed and/or refractory B-cell lymphoma who have had at least one prior cancer treatment.
Design:
Participants will be screened with:
Medical history
Physical exam
Assessment of how they do their daily activities
Blood and urine tests
Heart function test
Tissue biopsy (if needed)
Body imaging scans (may get a contrast agent through an intravenous (IV) catheter)
Participants will have a bone marrow aspiration and/or biopsy. A needle will be put into the hipbone. Bone marrow will be removed.
Participants may give blood, tissue, saliva, or cheek swab samples. They may have optional biopsies.
Screening tests will be repeated during the study.
Treatment will be given for up to 6 cycles. Each cycle lasts 21 days.
Participants will take venetoclax and prednisone tablets by mouth. They will take ibrutinib and lenalidomide capsules by mouth. They will get obinutuzumab and polatuzumab by IV infusion. They will keep a medicine diary.
Participants will visit the clinic 30 days after treatment ends. They will have follow-up visits for 5 years. If needed, they can visit their local doctor instead. They may be contacted by phone, mail, etc., for the rest of their life....
- Detailed 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 non-Hodgkin lymphoma (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-P targets major survival pathways in B-cell lymphomas including BCL-2 (apoptosis); BTK (B-cell receptor signaling and NF-kB); Cereblon (NF-kB) and CD20 with additional genotoxic stress from the anti-mitotic antibody-drug conjugate targeting CD79b, polatuzumab.
Objectives:
* To determine the maximum tolerated dose (MTD) and the safety and toxicity profile of polatuzumab and venetoclax in combination with ibrutinib, prednisone, obinutuzumab and Revlimid (lenalidomide) (ViPOR-P) in relapsed/refractory B-cell lymphomas
* To determine the complete response (CR) rate of ViPOR-P in relapsed/refractory non-GCB
DLBCL
Eligibility:
* Individuals \>= 18 years of age
* ECOG performance status of \<= 2
* Histologically or cytologically confirmed relapsed and/or refractory B-cell lymphoma, excluding mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
* Adequate organ function unless dysfunction secondary to lymphoma
Design:
* Open-label, single-center, non-randomized phase 1 study
* Standard 3 + 3 design will be used to determine the MTD of polatuzumab and venetoclax in combination with ibrutinib, prednisone, obinutuzumab and Revlimid (lenalidomide) (ViPOR-P) in relapsed/refractory B-cell lymphomas
* A small expansion cohort will be treated at the MTD for a further analysis of safety and preliminary activity.
* An expansion cohort of 32 patients (including 27 new patients + 5 patients already enrolled at DL3/MTD) with non-GCB DLBCL will be treated at the MTD to determine the CR rate to ViPOR-P of this aggressive lymphoma subtype.
* Maximum 6 cycles of combination targeted therapy every 21 days.
* To explore all dose levels in the phase 1 study and to assess the CR rate in non-GCB
DLBCL patients in a dose expansion at the MTD as well as to allow for the possibility of a few screen failures and inevaluable subjects, the accrual ceiling will be set at 55 patients.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 55
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1: Dose Escalation Revlimid Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax Arm 2: Dose Expansion Revlimid Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles) Arm 1: Dose Escalation Polatuzumab Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax Arm 2: Dose Expansion Polatuzumab Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles) Arm 1: Dose Escalation obinutuzumab Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax Arm 1: Dose Escalation prednisone Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax Arm 1: Dose Escalation venetoclax Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax Arm 1: Dose Escalation ibrutinib Venetoclax (PO) 800mg at escalating doses (2 dose levels) on days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at escalating doses (2 dose levels) on day 2 of each 21-day cycle (maximum 6 cycles) to determine MTD of polatuzumab and venetoclax Arm 2: Dose Expansion obinutuzumab Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles) Arm 2: Dose Expansion prednisone Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles) Arm 2: Dose Expansion ibrutinib Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles) Arm 2: Dose Expansion venetoclax Venetoclax (PO) at the MTD days 2-14, ibrutinib (PO) 560mg on days 1-14, prednisone (PO) 100mg on days 1-7, obinutuzumab 1000mg (IV) on days 1 and 2, lenalidomide (PO) 15mg on days 1-14, and polatuzumab (IV) at the MTD of each 21-day cycle (maximum 6 cycles)
- Primary Outcome Measures
Name Time Method Number and grade of adverse events 21 days Number and grade of adverse events
Complete response (CR) rate every 42 days for 3 assessments (e.g., every 2 cycles) and/or end of treatment Response rate based on Lugano Classification Response Criteria
- Secondary Outcome Measures
Name Time Method Overall survival (OS) time from the date of study enrollment until death from any cause, assessed every 3-6 months time from the date of study enrollment until death from any cause, assessed every 3-6 months
Overall Response Rate (ORR) time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6months time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6months
Event-free survival (EFS) time from the date of study enrollment until time of disease relapse, disease progression, alternative therapy for lymphoma given (such as radiation), or death, whichever occurs first, assessed every 3-6 months time from the date of study enrollment until time of disease relapse, disease progression, alternative therapy for lymphoma given (such as radiation), or death, whichever occurs first, assessed every 3-6 months
Duration of Response (DOR) For ORR-time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6months, For CR-time measurement criteria are met for CR For ORR-time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6months, For CR-time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented or death, assessed every 3-6months
Progression-free survival (PFS) time from date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months time from date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months
Complete response (CR) rate time measurement criteria are met for CR until the first date that progressive disease is objectively documented or death, assessed every 3-6months time measurement criteria are met for CR until the first date that progressive disease is objectively documented or death, assessed every 3-6months
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States