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VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) in 21-day cycles for up to 6 cycles

Obinutuzumab 1000 mg IV (intravenous) days 1 and 2 for a maximum of 6 cycles every 21 days (each cycle is 21 days)

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)

Mark J Roschewski, M.D.

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 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

CT, PDG PET, and 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.

Background:

* Primary diffuse large B-cell lymphoma of the CNS (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.

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

.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 dbGaP.

Success is defined as completing at least 2 cycles of VIPOR therapy without the need to discontinue treatment due to toxicity. The fraction of participants who achieve a success will be determined and reported along with a 95% confidence interval.

The complete response rate of up to 6 cycles of VIPOR in PCNSL and SCNSL will be reported along with a 95% confidence interval.

The overall response rate of up to 6 cycles of VIPOR in PCNSL and SCNSL will be reported along with a 95% confidence interval.

Overall survival (OS) after VIPOR in PCNSL and SCNSL will be determined using a Kaplan-Meier curve. The median will be determined and presented with its associated 95% confidence interval.

The progression-free survival (PFS) after VIPOR in PCNSL and 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.

The duration of response after VIPOR in PCNSL and 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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System	NCT05211336	Primary Diffuse... Aggressive B-ce...	Obinutuzumab Prednisone Lenalidomide Venetoclax Ibrutinib	18 Years -	National Institutes of Health Clinical Center (CC)
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (VIPOR) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System	NCT05211336	Primary Diffuse... Aggressive B-ce...	Obinutuzumab Prednisone Lenalidomide Venetoclax Ibrutinib	18 Years -	National Institutes of Health Clinical Center (CC)

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