Trials / Recruiting

RecruitingNCT06649812

Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma

A Phase 2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed or Refractory CD10-Negative Diffuse-Large B-Cell Lymphoma (DLBCL) and High-Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements (HGBCL-DH-BCL2)

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 120 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II trial tests how well venetoclax, ibrutinib, prednisone, obinutuzumab, and Revlimid® (ViPOR) works in treating patients with CD10 negative diffuse large B-cell lymphoma (DLBCL) and high-grade lymphoma with MYC and BCL2 rearrangements that has come back after a period of improvement (relapsed) and/or that has not responded to previous treatment (refractory). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ibrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. Anti-inflammatory drugs, such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Obinutuzumab, a monoclonal antibody, binds to a protein called CD20, which is found on B cells and some types of leukemia and lymphoma cells. Obinutuzumab may block CD20 and help the immune system kill cancer cells. Revlimid, a type of anti-angiogenesis agent and a type of immunomodulating agent, may help the immune system kill abnormal blood cells or cancer cells. It may also prevent the growth of new blood vessels that cancers need to grow. ViPOR may be an effective treatment option for patients with relapsed and/or refractory CD10 negative DLBCL and high-grade B-cell lymphoma with MYC and BCL2 rearrangements.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the complete response (CR) rate of ViPOR in relapsed/refractory (R/R): Ia. CD10-negative DLBCL; and Ib. CD10-positive or negative high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 (with or without BCL6) translocations (HGBCL-double hit \[DH\]-BCL2). SECONDARY OBJECTIVES: I. To evaluate the complete response (CR) rate of ViPOR in relapsed/refractory (R/R): Ia. CD10-negative activated B-cell (ABC) DLBCL; and Ib. CD10-negative non-ABC (i.e., unclassified or germinal center B-cell \[GCB\]) DLBCL. II. To evaluate the overall response rate (ORR), duration of response (DOR), event-free survival (EFS), time to progression (TTP), progression-free survival (PFS), overall survival (OS), and the safety \& toxicity profile of ViPOR in relapsed/refractory (R/R): IIa. CD10-negative ABC DLBCL; and IIb. CD10-negative non-ABC (i.e., unclassified or GCB) DLBCL; and IIc. CD10-positive or negative HGBCL-DH-BCL2. EXPLORATORY OBJECTIVES: I. To assess response and outcome to ViPOR based on molecular DLBCL subtype by cell-of-origin (COO) testing using Lymph2Cx gene-expression profiling (GEP). II. To assess response and outcome to ViPOR based on genetic DLBCL subtype by LymphGen classification using whole exome sequencing (WES), whole genome sequencing (WGS), and ribonucleic acid (RNA)-sequencing (RNA-seq). III. To determine other molecular correlates of response or resistance to ViPOR therapy. IV. To determine early molecular correlates of response or resistance as well as the rate of complete molecular remission, as determined by assays for circulating-tumor deoxyribonucleic acid (DNA) (ctDNA). OUTLINE: Patients receive venetoclax orally (PO) once daily (QD) on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab intravenously (IV) on days 1 and 2, and lenalidomide (Revlimid) PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, positron emission tomography (PET), computed tomography (CT) and/or magnetic resonance imaging (MRI) and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study. After completion of study treatment, patients are followed up every 6 months for 2 years, yearly during years 3-5, and then for survival for up to 10 years from the date of registration.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo optional tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Ibrutinib	Given PO
DRUG	Lenalidomide	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Obinutuzumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET
DRUG	Prednisone	Given PO
DRUG	Venetoclax	Given PO

Timeline

Start date: 2025-10-07
Primary completion: 2027-09-01
Completion: 2027-09-01
First posted: 2024-10-21
Last updated: 2026-04-16

Locations

82 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06649812. Inclusion in this directory is not an endorsement.