Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid in Combination With Polatuzumab (ViPOR-P) in Relapsed/Refractory B-cell Lymphoma
Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid in Combination With Polatuzumab (ViPOR-P) in Relapsed/Refractory B-cell Lymphoma
2 other identifiers
interventional
55
1 country
1
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....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 lymphoma
Started Jul 2021
Longer than P75 for phase_1 lymphoma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2021
CompletedFirst Posted
Study publicly available on registry
February 5, 2021
CompletedStudy Start
First participant enrolled
July 9, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 18, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 18, 2031
April 29, 2026
April 27, 2026
4.9 years
February 4, 2021
April 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number and grade of adverse events
Number and grade of adverse events
21 days
Complete response (CR) rate
Response rate based on Lugano Classification Response Criteria
every 42 days for 3 assessments (e.g., every 2 cycles) and/or end of treatment
Secondary Outcomes (6)
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
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
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
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
Overall survival (OS)
time from the date of study enrollment until death from any cause, assessed every 3-6 months
- +1 more secondary outcomes
Study Arms (2)
Arm 1: Dose Escalation
EXPERIMENTALVenetoclax (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
EXPERIMENTALVenetoclax (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)
Interventions
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
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
administered orally, days 1 and 14, at a dose of 15 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
administered intravenously, on day 2, at varying doses of 1.4-1.8 mg/kg (based upon assigned dose level); every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
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
administered orally, days 2-14, at a dose of 800 mg; every 21 days for up to 6 cycles, or until disease progression or unacceptable toxicity
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed B-cell lymphoma confirmed by the Laboratory of Pathology, NCI, as follows:
- Cohorts 1 and 2:
- 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: with the following exceptions:
- MCL is excluded given increased risk of tumor lysis syndrome (TLS) with venetoclax compared to other non-Hodgkin lymphomas and need for venetoclax ramp-up, dose-escalation.
- CLL/SLL is excluded given alternative dosing of FDA-approved venetoclax for relapsed CLL/SLL and increased risk of TLS with CLL/SLL compared to other non-Hodgkin lymphomas.
- Cohort 3:
- Non-GCB DLBCL: includes DLBCL NOS and subtypes, transformed lymphoma, THRLBCL, as well as high-grade B-cell lymphoma with MYC and/or BCL6 rearrangement(s).
- NOTE: Patients with known active CNS lymphoma are not eligible.
- Relapsed and/or refractory disease after at least 1 prior treatment regimen, as follows:
- Aggressive B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anthracycline-containing regimen
- Indolent B-cell lymphoma: relapsed after and/or refractory to at least 1 prior anti- CD20 antibody-containing regimen.
- Patients must have evaluable disease by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on CT or MRI and/or evaluable FDG-avid lesions on PET).
- NOTE: Lesions that have been irradiated cannot be included in the tumor assessment unless unequivocal tumor progression has been documented in these lesions after radiation therapy.
- Age \>=18 years
- +38 more criteria
You may not qualify if:
- The following restrictions apply to current or prior anti-cancer treatment, prior to the first dose of study drug:
- Patients who are actively receiving any other investigational agents.
- Any chemotherapy or anti-cancer antibodies within 2 weeks. NOTE: Short courses of corticosteroids or palliative XRT prior to enrollment are permitted within the 2- week washout period.
- Radio- or toxin-immunoconjugates within 10 weeks.
- Previous treatment with more than one of the study agents (i.e., polatuzumab, venetoclax, ibrutinib, or Revlimid(R)), excluding prior prednisone or anti-CD20 antibody treatment.
- Prior allogeneic stem cell (or other organ) transplant within 6 months or any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days.
- Not recovered (i.e., \<= Grade 1 or baseline) from adverse events due to previously administered anti-cancer treatment, surgery, or procedure. NOTE: Exceptions to this include events not considered to place the subject at unacceptable risk of participation in the opinion of the PI (e.g., alopecia).
- Patients requiring the use of warfarin are excluded because of potential drug-drug interactions that may potentially increase the exposure of warfarin.
- Patients requiring the following agents to the first dose of venetoclax or ibrutinib are excluded, as noted:
- Strong CYP3A inhibitors within 7 days
- Strong CYP3A inducers within 7 days
- NOTE: Moderate CYP3A inhibitors and inducers should be used with caution and an alternative medication used, whenever possible.
- Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator:
- Symptomatic congestive heart failure, unstable angina pectoris, or uncontrolled cardiac arrhythmia
- Uncontrolled and/or symptomatic thyroid disease
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher J Melani, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 4, 2021
First Posted
February 5, 2021
Study Start
July 9, 2021
Primary Completion (Estimated)
June 18, 2026
Study Completion (Estimated)
June 18, 2031
Last Updated
April 29, 2026
Record last verified: 2026-04-27
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data will be available during the study and indefinitely.@@@@@@@@@@@@Genomic data will be available once genomic data are uploaded per protocol GDS plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data will be made available via dbGaP through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP. @@@@@@@@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.