Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS)Phase 1NCT05211336
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System
A Phase 1 study testing Obinutuzumab, Prednisone and Lenalidomide in people with Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS) and Aggressive B-cell Lymphoma With Secondary Involvement of the CNS, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS), Aggressive B-cell Lymphoma With Secondary Involvement of the CNS
- What is being tested?
- Obinutuzumab, Prednisone and Lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2022to 1 Jun 2029
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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)
- Aspartate Aminotransferase or serum glutamic oxaloacetic transaminase/ Alanine Aminotransferase or serum glutamic pyruvic transaminase AST(SGOT)/ALT(SGPT) <= 3.0 X institutional ULN for those without lymphoma involvement OR <= 5.0 X institutional ULN for those with lymphoma involvement
- Serum Creatinine OR creatinine clearance (Cr Cl) <= 1.5 mg/dL OR > 40 ml/min/1.73m^2
- NOTE: Cr Cl will be calculated with the use of the 24-hour creatinine clearance or estimated glomerular filtration rate (eGRF) in the clinical lab
- Laboratory assessments to determine eligibility may be performed at Clinical Laboratory Improvement Amendments (CLIA) (or equivalent) certified laboratories outside the National Institutes of Health (NIH) and results forwarded to the study team for review and management. Given that the methodologies utilized are similar across all laboratories, no significant variability is expected and there is no anticipation that study data will be affected. However, as different laboratories use slightly different kinds of equipment, each laboratory must determine/validate its own reference ranges. Therefore, on this protocol, normal ranges from each lab will be used in reference to terms such as upper limit of normal (ULN), except in cases where absolute values are appropriate and are specified as such
- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) must be < 1.5 x the ULN; except if, the aPTT is prolonged because of a positive Lupus Anticoagulant.
- Male and female participants must agree to use certain methods of birth control. A highly effective method of birth control for female participants is defined as a method that has a low failure rate (i.e., less than 1% per year) when used consistently and correctly and includes implants, injectables, birth control pills with two hormones, some intrauterine devices (IUDs). Male participant cannot use highly effective methods and are required to use barrier. The specific guidelines are as follows:
- Women: Females of childbearing potential (FOCBP), defined as a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months), must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Revlimid (R), as well as for the duration after the last dose of study drug as listed below.
- Men: Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures to prevent pregnancy of their partner and should also agree to not donate sperm while taking the study treatment and for the durations as listed below.
- Contraception Requirements
- Time frame/Study Drug/Women/Men
- Pre-Treatment/During Treatment: Time frame prior to/during dosing:
- All drugs: Begins 28 days prior to treatment/Begins on day 1
- Post-Treatment: Time frame after the last dose:
- Venetoclax: 90 days/90 days
- Ibrutinib: 3 months/3 months
- Obinutuzumab: 18 months/6 months
- Revlimid (R): 28 days/28 days
- All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS)(TM) program and be willing and able to comply with the requirements of Revlimid REMS(TM).
- Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through designated time points after study drugs discontinuation (as required for women contraception in the table above)
Who cannot join
- 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
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- 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)
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System
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.
Read more
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.
Read the detailed description
Background:
- Primary diffuse large B-cell lymphoma of the central nervous system (CNS) primary central nervous system lymphoma (PCNSL) and aggressive B-cell lymphomas with secondary CNS involvement (SCNSL) have a poor prognosis
- Most CNS lymphomas (CNSL) exhibit molecular biology features of activated B cell diffuse large B-cell lymphoma (ABC DLBCL)
- We developed VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide [Revlimid (Registered Trademark)]) treatment in systemic lymphomas as a platform most effective for ABC DLBCL
- All agents in the VIPOR combination achieve meaningful CNS penetration and clinical activity for lymphomas involving the CNS
Objective:
-To determine the safety and tolerability of VIPOR in participants with PCNSL and SCNSL
Eligibility:
- Primary diffuse large B-cell lymphoma of the CNS (PCNSL) or non-germinal center B-cell (non-GCB) diffuse large B-cell lymphoma with secondary involvement of the CNS (SCNSL)
- Relapsed/refractory after prior therapy or ineligible for standard frontline therapy
- Age >= 18 years
- No pregnant women
- Adequate organ function
Study Design:
- A safety study of 10 evaluable participants with PCNSL or SCNSL treated with VIPOR (the original study protocol enrolled 4 participants to Cohort 1, Arm 1 consisting of VIPOR plus nivolumab which is now closed).
- Participants will receive VIPOR in 21-day cycles for a maximum of 6 cycles to collect data on safety and efficacy.
- Accrual ceiling will be set at 16 participants to allow for a few inevaluable participants or screen failures.
- Conditions
- Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS), Aggressive B-cell Lymphoma With Secondary Involvement of the CNS
- Being tested
- Obinutuzumab, Prednisone, Lenalidomide, Venetoclax, Ibrutinib
- Keywords
- CNS, PCNSL, SCNSL, Systemic Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObinutuzumabDrug
Also called Gazyva
Obinutuzumab 1000 mg IV (intravenous) days 1 and 2 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
PrednisoneDrug
Also called Rayos, Deltasone, Prednisone Intensol
Prednisone 100 mg PO (by mouth) daily days 1-7 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
LenalidomideDrug
Also called REVLIMID
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)
VenetoclaxDrug
Also called Venclexta, Venclyxto
Venetoclax 800 mg PO (by mouth) on days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
IbrutinibDrug
Also called Imbruvica
Ibrutinib 560 mg PO (by mouth) daily days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days)
AcetaminophenDrug
Also called Tylenol, Ofirmev, FeverAll
650 mg by mouth (PO) daily on days 1 and 2 approximately 30-60 minutes prior to Obinutuzumab infusion.
DiphenhydramineDrug
Also called Benadryl, Banophen, Nytol
50mg by mouth (PO) daily on days 1 and 2 approximately 30-60 minutes prior to Obinutuzumab infusion.
Peg-filgrastimOther
Also called Neulasta
6 mg subcutaneous once on day 8 only.
CT Scan (chest, abdomen, and pelvis)Diagnostic test
Also called Computed tomography scan
To assess sites of disease.
MRIDiagnostic test
Also called Magnetic resonance imaging
If clinically indicated.
18f-FDG-PETDiagnostic test
Also called F18-fluorodeoxyglucose-positron emission tomography
If clinically indicated.
PETDiagnostic test
If clinically indicated.
Lumbar puncture/Ommaya tapDiagnostic test
If clinically indicated.
Bone marrow aspiration/biopsyDiagnostic test
If clinically indicated.
EKGCombination product
Also called Electrocardiogram
To determine eligibility.
| Study group | Role | What they receive |
|---|---|---|
| 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) | Experimental | VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) in 21-day cycles for up to 6 cycles Receives: Drug: Obinutuzumab; Drug: Prednisone; Drug: Lenalidomide; Drug: Venetoclax; Drug: Ibrutinib; Drug: Acetaminophen; Drug: Diphenhydramine; Other: Peg-filgrastim; Diagnostic Test: CT Scan (chest, abdomen, and pelvis); Diagnostic Test: MRI; Diagnostic Test: 18f-FDG-PET; Diagnostic Test: PET; Diagnostic Test: Lumbar puncture/Ommaya tap; Diagnostic Test: Bone marrow aspiration/biopsy; Combination Product: EKG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 2 Cycles (each cycle is 21 days)
Secondary outcomes (5)
Complete Response (CR)
Complete response is disappearance of all detectable evidence of disease and disease-related symptoms measured by the Lugano criteria. The complete response rate of up to 6 cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) in primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) will be reported along with a 95% confidence interval.
Measured: After cycles 3 and 6
Proportion of Participants Overall Response Rate (Complete Response + Partial Response) to VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide)
The overall response rate of up to 6 cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) in primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) will be reported along with a 95% confidence interval. Complete response (CR) + Partial response (PR) was measured by the Lugano criteria. Complete response is disappearance of all detectable evidence of disease and disease-related symptoms. Partial response is a ≥50% decrease in the sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
Measured: After cycles 3 and 6
Overall Survival (OS)
Overall survival (OS) is defined as the duration of time from the date of study enrollment until time of death from any cause, or 10 years post-treatment whichever occurs first. Overall survival (OS) after VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) in primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) will be determined using a Kaplan-Meier curve. The median will be determined and presented with its associated 95% confidence interval.
Measured: Up to 2.6 years
Progression Free Survival (PFS)
Progression-free survival (PFS) is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, death, or 10 years post-treatment, whichever occurs first. The progression-free survival (PFS) after VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) in primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) will be estimated using progression or death without progression as events, using a Kaplan-Meier curve. The median will be determined and presented with its associated 95% confidence interval. Progression was measured by the Lugano criteria and is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy, even if other lesions are decreasing in size.
Measured: Up to 2.6 years
Duration of Response (DOR)
The duration of response after VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) in primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) will be determined starting at the date a response is identified and will be estimated using a Kaplan-Meier curve along with a median DOR, and its associated 95% confidence interval. The duration of response (DOR) is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, death, or, in the absence of progressive disease (PD), date of last assessment. CR is disappearance of all detectable evidence of disease and disease-related symptoms. PR is a ≥50% decrease in the sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progression is appearance of any new nodal lesion.
Measured: From date of first response until the date of recurrent or progressive disease is objectively documented, up to a max 2.6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start19 Apr 2022
- Primary completion1 Jun 2024
- Study completion1 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS)Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Rahul Lakhotia, National Cancer Institute (NCI)
- Investigators
- Rahul Lakhotia, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05211336
- Sponsor's protocol ID
- 10000516
- Other IDs
- 000516-C
- Status last verified
- Dec 2025
- First submitted
- 26 Jan 2022
- Last updated
- 8 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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).
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System
- ClinicalTrials.gov ID
- NCT05211336
- Acronym / sponsor ID
- 10000516
- Conditions
- Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS), Aggressive B-cell Lymphoma With Secondary Involvement of the CNS
- Keywords
- CNS, PCNSL, SCNSL, Systemic Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Apr 2022 (actual)
- Primary completion
- 1 Jun 2024 (actual)
- Study completion
- 1 Jun 2029 (estimated)
- First posted
- 27 Jan 2022 (actual)
- Results
- Posted 20 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Primary diffuse large B-cell lymphoma of the central nervous system (CNS) primary central nervous system lymphoma (PCNSL) and aggressive B-cell lymphomas with secondary CNS involvement (SCNSL) have a poor prognosis
- Most CNS lymphomas (CNSL) exhibit molecular biology features of activated B cell diffuse large B-cell lymphoma (ABC DLBCL)
- We developed VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide [Revlimid (Registered Trademark)]) treatment in systemic lymphomas as a platform most effective for ABC DLBCL
- All agents in the VIPOR combination achieve meaningful CNS penetration and clinical activity for lymphomas involving the CNS
Objective:
-To determine the safety and tolerability of VIPOR in participants with PCNSL and SCNSL
Eligibility:
- Primary diffuse large B-cell lymphoma of the CNS (PCNSL) or non-germinal center B-cell (non-GCB) diffuse large B-cell lymphoma with secondary involvement of the CNS (SCNSL)
- Relapsed/refractory after prior therapy or ineligible for standard frontline therapy
- Age >= 18 years
- No pregnant women
- Adequate organ function
Study Design:
- A safety study of 10 evaluable participants with PCNSL or SCNSL treated with VIPOR (the original study protocol enrolled 4 participants to Cohort 1, Arm 1 consisting of VIPOR plus nivolumab which is now closed).
- Participants will receive VIPOR in 21-day cycles for a maximum of 6 cycles to collect data on safety and efficacy.
- Accrual ceiling will be set at 16 participants to allow for a few inevaluable participants or screen failures.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) | Experimental | Drug: Obinutuzumab, Drug: Prednisone, Drug: Lenalidomide, Drug: Venetoclax, Drug: Ibrutinib, Drug: Acetaminophen, Drug: Diphenhydramine, Other: Peg-filgrastim, Diagnostic Test: CT Scan (chest, abdomen, and pelvis), Diagnostic Test: MRI, Diagnostic Test: 18f-FDG-PET, Diagnostic Test: PET, Diagnostic Test: Lumbar puncture/Ommaya tap, Diagnostic Test: Bone marrow aspiration/biopsy, Combination Product: EKGVIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) in 21-day cycles for up to 6 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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:
- 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).
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObinutuzumabAlso: GazyvaObinutuzumab 1000 mg IV (intravenous) days 1 and 2 for a maximum of 6 cycles every 21 days (each cycle is 21 days) | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| PrednisoneAlso: Rayos, Deltasone, Prednisone IntensolPrednisone 100 mg PO (by mouth) daily days 1-7 for a maximum of 6 cycles every 21 days (each cycle is 21 days) | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| LenalidomideAlso: REVLIMIDLenalidomide 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) | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| VenetoclaxAlso: Venclexta, VenclyxtoVenetoclax 800 mg PO (by mouth) on days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days) | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| IbrutinibAlso: ImbruvicaIbrutinib 560 mg PO (by mouth) daily days 1-14 for a maximum of 6 cycles every 21 days (each cycle is 21 days) | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| AcetaminophenAlso: Tylenol, Ofirmev, FeverAll650 mg by mouth (PO) daily on days 1 and 2 approximately 30-60 minutes prior to Obinutuzumab infusion. | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| DiphenhydramineAlso: Benadryl, Banophen, Nytol50mg by mouth (PO) daily on days 1 and 2 approximately 30-60 minutes prior to Obinutuzumab infusion. | Drug | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| Peg-filgrastimAlso: Neulasta6 mg subcutaneous once on day 8 only. | Other | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| CT Scan (chest, abdomen, and pelvis)Also: Computed tomography scanTo assess sites of disease. | Diagnostic test | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| MRIAlso: Magnetic resonance imagingIf clinically indicated. | Diagnostic test | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| 18f-FDG-PETAlso: F18-fluorodeoxyglucose-positron emission tomographyIf clinically indicated. | Diagnostic test | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| PETIf clinically indicated. | Diagnostic test | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| Lumbar puncture/Ommaya tapIf clinically indicated. | Diagnostic test | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| Bone marrow aspiration/biopsyIf clinically indicated. | Diagnostic test | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
| EKGAlso: ElectrocardiogramTo determine eligibility. | Combination product | 1: VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) |
Primary outcome
Proportion of Participants Who Completed at Least 2 Cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) Therapy Without Stopping Due to Toxicity
Time frame: After 2 Cycles (each cycle is 21 days)
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.
5 secondary outcomes
Complete Response (CR)
Time frame: After cycles 3 and 6
Proportion of Participants Overall Response Rate (Complete Response + Partial Response) to VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide)
Time frame: After cycles 3 and 6
Overall Survival (OS)
Time frame: Up to 2.6 years
Progression Free Survival (PFS)
Time frame: Up to 2.6 years
Duration of Response (DOR)
Time frame: From date of first response until the date of recurrent or progressive disease is objectively documented, up to a max 2.6 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rahul Lakhotia, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Obinutuzumab, Prednisone and Lenalidomide in people with Primary Diffuse Large B-cell Lymphoma of the Central Nervous System (CNS) and Aggressive B-cell Lymphoma With Secondary Involvement of the CNS, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Who Completed at Least 2 Cycles of VIPOR (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide) Therapy Without Stopping Due to Toxicity (time frame: After 2 Cycles (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.