Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System
Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System
2 other identifiers
interventional
14
1 country
1
Brief Summary
Background: People with primary diffuse large B-cell lymphoma of the central nervous system (CNS) and aggressive B-cell lymphomas with secondary CNS involvement have a poor prognosis. Researchers want to learn if a combination of drugs can help. Objective: To learn if it is safe to give people with these cancers Nivolumab (VIPOR-Nivo). Eligibility: People aged 18 and older with B-cell lymphoma in the CNS that does not respond to treatment, response to treatment does not last long, or there is no standard treatment. Design: Participants will be screened with: Health history Physical exam Blood, urine, and heart tests Computed tomography (CT), fludeoxyglucose F18 (FDG) positron emission tomography (PET), and magnetic resonance imaging (MRI) scans. Participants will lie in scanners that take pictures of the body. For some scans, a contrast or chemical agent will be injected into a vein. Lumbar puncture or Ommaya tap. Participants will have a small needle inserted into their lower back or scalp to obtain fluid. Possible tumor biopsy. Participants will have a needle inserted into a tumor to take a sample. Participants will get the study drugs in 21-day cycles. They may have up to 6 treatment cycles. They will take some drugs by infusion into a vein and some drugs by mouth. Participants will get counseling at least every 28 days on the risks of lenalidomide. Participants will have visits throughout the study. Visits may include repeats of the screening tests. They may also include: Bone marrow biopsy. Participants will have a needle inserted into their hipbone to remove marrow. Saliva samples and cheek swabs Participants will have periodic follow-up visits for about 10 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Apr 2022
Longer than P75 for phase_1
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
January 26, 2022
CompletedFirst Posted
Study publicly available on registry
January 27, 2022
CompletedStudy Start
First participant enrolled
April 19, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2024
CompletedResults Posted
Study results publicly available
April 20, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2029
ExpectedJanuary 8, 2026
December 1, 2025
2.1 years
January 26, 2022
March 18, 2025
December 23, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of Participants Who Completed at Least 2 Cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) Therapy Without Stopping Due to Toxicity
The proportion of participants who complete at least 2 cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) therapy without stopping due to toxicity will be determined and reported along with a 95% confidence interval. Success is defined as completing at least 2 cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) therapy without the need to discontinue treatment due to toxicity (i.e., serious adverse event). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
After 2 Cycles (each cycle is 21 days)
Secondary Outcomes (5)
Complete Response (CR)
After cycles 3 and 6
Proportion of Participants Overall Response Rate (Complete Response + Partial Response) to VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide)
After cycles 3 and 6
Overall Survival (OS)
Up to 2.6 years
Progression Free Survival (PFS)
Up to 2.6 years
Duration of Response (DOR)
From date of first response until the date of recurrent or progressive disease is objectively documented, up to a max 2.6 years
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Adverse events were monitored/assessed from the date of first dose of any study drug, through 30 days after the last dose of any study drug after the last dose of any study drug. Participants were followed for a maximum duration of 2.6 years.
Study Arms (1)
1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide)
EXPERIMENTALVIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) in 21-day cycles for up to 6 cycles
Interventions
Obinutuzumab 1000 mg IV (intravenous) days 1 and 2 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
50mg by mouth (PO) daily on days 1 and 2 approximately 30-60 minutes prior to Obinutuzumab infusion.
6 mg subcutaneous once on day 8 only.
To assess sites of disease.
If clinically indicated.
If clinically indicated.
If clinically indicated.
If clinically indicated.
If clinically indicated.
To determine eligibility.
Prednisone 100 mg PO (by mouth) daily days 1-7 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
Lenalidomide 10 or 15 mg PO (by mouth) on days 1-14 for 1 cycle (21 days); followed by Lenalidomide 10 or 15 mg PO daily days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
Venetoclax 800 mg PO (by mouth) on days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
Ibrutinib 560 mg PO (by mouth) daily days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
650 mg by mouth (PO) daily on days 1 and 2 approximately 30-60 minutes prior to Obinutuzumab infusion.
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed primary diffuse large B-cell lymphoma of the central nervous system (CNS) primary central nervous system lymphoma (PCNSL) or non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma with secondary involvement of the CNS (SCNSL). NOTE: Participants with B-cell lymphomas that were previously indolent but now involve the CNS (i.e., transformed from previous follicular lymphoma, chronic lymphocytic leukemia, marginal zone lymphoma, and mantle cell lymphoma) are eligible.
- Participants must have a disease that is relapsed or refractory after initial systemic treatment or be considered ineligible for standard frontline therapy with high-dose methotrexate due to one of the following criteria:
- Age\>= 70 years
- Estimated glomerular filtration rate \< 60 ml/min/1.73m\^2
- Presence of ascites or pleural effusion
- Participants must have evaluable disease by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.) and/or imaging (measurable lymph nodes or masses on computed tomography (CT) or magnetic resonance imaging (MRI) and/or evaluable fluorodeoxyglucose (FDG)-avid lesions on positron emission tomography (PET).
- Participants with second malignancies not requiring active systemic therapy or premalignant conditions such as monoclonal B-cell lymphocytosis (MBL) or monoclonal gammopathy of undetermined significance (MGUS) are eligible.
- Participants that are positive for hepatitis B core antibody (HBcAb), hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative hepatitis B and/or C viral load by polymerase chain reaction (PCR).
- Age \>=18 years
- Eastern Cooperative Oncology Group (ECOG) performance status \<=2. NOTE: In participants with neurologic deficits caused by CNS lymphoma any ECOG status is acceptable to be eligible.
- Participants must have adequate organ and marrow function as defined below:
- absolute neutrophil count \>= 1000 cells/mcL (1 X 10\^9/L)
- platelet count \>= 50,000 cells/mcL (50 X 10\^9/L)
- hemoglobin \> 8.0 g/dL (transfusions permitted)
- total bilirubin \<= 1.5 X upper limit of normal (ULN) (unless Gilbert's syndrome or disease infiltration of the liver is present)
- +19 more criteria
You may not qualify if:
- Participants with plasmablastic lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma are not eligible.
- Chemotherapy (excluding corticosteroids), radiation therapy, and/or monoclonal antibody \<=7 days prior to first administration of study treatment. Rationale for a short 7-day window is that participants with relapsed CNS lymphomas often have existing neurologic conditions that mandate urgent therapy.
- Previous treatment with more than one of the following classes of medications: (1) Bruton's tyrosine kinase (BTK) inhibitors, (2) B-cell lymphoma 2 (Bcl-2) inhibitors, (3) immunomodulatory imide drugs (IMIDs) (including lenalidomide and pomalidomide).
- Participants who require continuous treatment with a strong cytochrome P450 family 3, subfamily A (CYP3A) inhibitor/inducer (i.e., with the exception of any medication to be specifically studied in this protocol).
- NOTE: A comprehensive list of inhibitors, inducers, and substrates may be found at: https://drug-interactions.medicine.iu.edu/MainTable.aspx
- Human immunodeficiency virus (HIV)-positive participants
- Pregnant women- a pregnancy test (urine or serum) with a sensitivity of 25 mIU/mL must be done at screening.
- Participants with second malignancies requiring active systemic therapy are excluded.
- Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification
- History of any ventricular arrhythmia
- Unable to swallow capsules, or disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Uncontrolled ongoing or active infection
- Concomitant use of warfarin or other vitamin K antagonists
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
- Currently active, clinically significant hepatic impairment (\>= moderate hepatic impairment according to the National Cancer Institute (NCI)/Child Pugh classification)
- +1 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
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Rahul Lakhotia
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Rahul Lakhotia, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 26, 2022
First Posted
January 27, 2022
Study Start
April 19, 2022
Primary Completion
June 1, 2024
Study Completion (Estimated)
June 1, 2029
Last Updated
January 8, 2026
Results First Posted
April 20, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All IPD recorded in the medical record will be shared with intramural investigators upon request. All large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).