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ViPOR combination therapy for relapsed 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)

Phase 2 Interventional National Cancer Institute (NCI) · NCT06649812

This treatment will try a five‑drug targeted combination called ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide) in adults whose aggressive B‑cell lymphoma has relapsed or not responded to prior therapy, focusing on specific genetic subtypes like CD10‑negative DLBCL and high‑grade B‑cell lymphoma with MYC/BCL2 rearrangements.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionsibrutinib, CAR-T, chimeric antigen receptor, chemotherapy, radiation, obinutuzumab, prednisone
Locations83 sites (Tucson, Arizona and 82 other locations)
Trial IDNCT06649812 on ClinicalTrials.gov

What this trial studies

This is a phase II trial testing the ViPOR combination in adults with relapsed or refractory aggressive B‑cell lymphomas, with separate cohorts for CD10‑negative DLBCL and for high‑grade B‑cell lymphoma with MYC/BCL2 rearrangements. The primary endpoint is complete response (CR) rate in the prespecified cohorts, with secondary endpoints including overall response rate, duration of response, progression‑free and overall survival, and safety. The protocol includes serial biopsies, bone marrow assessment, imaging, and comprehensive molecular profiling using Lymph2Cx gene‑expression profiling and LymphGen classification from WES/WGS/RNA‑seq to correlate genetics with outcome. Exploratory aims seek molecular markers of response or resistance to guide future targeted therapy choices.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed relapsed or refractory aggressive B‑cell lymphoma who meet the specified pathology criteria—primarily CD10‑negative DLBCL cohorts or high‑grade B‑cell lymphoma with MYC and BCL2 rearrangements—confirmed by the site principal investigator.

Not a fit: Patients whose lymphoma does not match the required molecular or pathologic subtypes, those with significant organ dysfunction or comorbidities that prevent multi‑drug therapy, or those unable to undergo required biopsies and visits may not receive benefit from this regimen.

Why it matters

Potential benefit: If successful, ViPOR could raise complete response rates and prolong remissions in patients with relapsed or refractory genetically defined aggressive B‑cell lymphomas.

How similar studies have performed: Components of ViPOR (venetoclax, ibrutinib, obinutuzumab, lenalidomide) and some smaller combinations have shown activity in B‑cell lymphomas, but the full five‑drug ViPOR regimen is novel and not yet proven in large trials.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Patient must be ≥ 18 years of age
* Patient must have histologically or cytologically confirmed aggressive B-cell lymphoma as follows:

  * Cohort 1: CD10-negative DLBCL, which includes:

    * CD10-negative non-GCB DLBCL, not otherwise specified (NOS) (i.e., CD10-/BCL6- or CD10-/BCL6+/MUM1+ DLBCL)
    * CD10-negative GCB DLBCL, NOS (i.e., CD10-/BCL6+/MUM1- DLBCL)
    * CD10-negative HGBCL with MYC and BCL6 (without BCL2) translocations (HGBCL-DH-BCL6)
    * CD10-negative HGBCL, NOS (without MYC and BCL2 translocations)
    * CD10-negative T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) OR
  * Cohort 2: CD10-positive or negative HGBCL with MYC and BCL2 rearrangements (with or without BCL6 rearrangement) (HGBCL-DH-BCL2)

    * NOTE: The site principal investigator must review and verify the pathology report findings to ensure the patient is eligible and is assigned to the respective cohort at the time of registration
* Patient must have relapsed and/or refractory disease after at least 1 prior anthracycline and anti-CD20 antibody-containing regimen
* Patient must not have confirmed or suspected primary mediastinal large B-cell lymphoma (PMBL)
* Patient must not be pregnant due to the potential harm to an unborn fetus with the treatment regimens being used.

  * All patients of childbearing potential must have a serum or urine study with a sensitivity of at least 25 mIU/mL within 14 days prior to registration to rule out pregnancy and again within 24 hours prior to starting cycle 1 day 1 of treatment.
  * A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) 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)
* Patients of childbearing potential must not expect to conceive children by abstaining from sexual intercourse or by using accepted and effective methods of contraception throughout the entire duration of protocol treatment, including during dose interruptions, and for 6 months after the last dose of protocol treatment. Male patients must not father children by abstaining from sexual intercourse or by using a condom during sexual contact with pregnant partners or partners of childbearing potential throughout the entire duration of protocol treatment, including dose interruptions, and for 6 months after the last dose of protocol treatment even if they have had a successful vasectomy
* Male patients must agree to not donate semen or sperm during the entire duration of protocol treatment or for at least 28 days after the last dose of lenalidomide
* Patient must agree to abstain from breastfeeding during the entire duration of protocol treatment and for at least 6 months after the last dose of protocol treatment
* Patient must agree to abstain from donating blood during the entire duration of protocol treatment and for at least 28 days after the last dose of lenalidomide
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Absolute neutrophil count (ANC) ≥ 1,000/mcL without requirement for granulocyte colony stimulating factor (G-CSF) support (obtained ≤ 7 days prior to registration)
* Hemoglobin ≥ 8 g/dL (obtained ≤ 7 days prior to registration)
* Platelets ≥ 75,000/mcL without requirement for platelet transfusion support (obtained ≤ 7 days prior to registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 3.0 x institutional ULN for patients with documented Gilberts syndrome) (obtained ≤ 7 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x institutional ULN (obtained ≤ 7 days prior to registration)
* Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m\^2 (estimated by Cockcroft-Gault method or measured) (obtained ≤ 7 days prior to registration)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patient must not have confirmed or suspected primary DLBCL of the central nervous system (CNS) (PCNSL)
* Patients with history of secondary CNS lymphoma (SCNSL) are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have taken or require warfarin or other strong CYP3A inhibitors or inducers within 7 days prior to registration.

  * NOTE: Antiplatelet agents, other anticoagulants aside from warfarin, as well as mild or moderate CYP3A inhibitors or inducers are permitted on study but should be used with caution
* Patient must not have an uncontrolled intercurrent illness that would interfere with the safety or efficacy assessment of this protocol
* Patient must not have evidence of an active infection at the time of registration
* Patient must not have the following current or prior anti-cancer treatment:

  * Any chemotherapy, targeted therapy, anti-cancer antibodies, antibody-drug conjugates, or bi-specific antibodies received within 2 weeks prior to registration

    * NOTE: Short courses of corticosteroids or palliative external beam radiation therapy (XRT) prior to registration are permitted
  * More than 3 prior lines of cytotoxic chemotherapy, excluding targeted therapy, anti-cancer antibodies, antibody-drug conjugates, bi-specific antibodies, and radio- or toxin-immunoconjugates

    * NOTE: Cytoreductive chemotherapy followed by autologous stem cell transplant (ASCT) counts as 1 line of cytotoxic therapy. Similarly, cytoreductive chemotherapy (either pre-T-cell collection or as bridging therapy) followed by pre-conditioning therapy/chimeric antigen receptor T-cell (CAR-T) counts as 1 line of therapy, as long as no disease progression occurs between interventions. For both therapies, if progressive disease is documented between 2 distinct regimens, then they should be counted as 2 lines of cytotoxic chemotherapy
  * Radio- or toxin-immunoconjugates within 10 weeks prior to registration
  * Previous treatment with more than one of the following study agents: venetoclax, ibrutinib, or lenalidomide
  * Prior autologous stem cell transplant (ASCT), chimeric antigen receptor T-cell (CAR-T) therapy, or allogeneic stem cell (or other organ) transplant within 3 months prior to registration
  * Any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to registration

    * NOTE: In addition, patient must have recovered (i.e., ≤ grade 1 or baseline) from all adverse events due to previously administered anti-cancer treatment, surgery, or procedure
    * NOTE: Exceptions to this include events not considered to place the patient at unacceptable risk of participation in the opinion of the treating investigator (i.e., alopecia)
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must have adequate formalin fixed paraffin embedded (FFPE) tumor tissue specimen from the initial diagnostic biopsy or on-study repeat tumor tissue biopsy for molecular analysis

  * NOTE: Excisional tumor biopsy is preferred. Core needle biopsies will be considered adequate if there is enough tissue for the mandatory molecular analysis. Submission of an entire FFPE tumor block is preferred, but if unavailable 10 x 10um FFPE scrolls may be submitted as an alternative. If adequate archived FFPE tumor tissue is unavailable, the patient must be willing to undergo research biopsy for molecular analysis
* Patient must have measurable disease
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Where this trial is running

Tucson, Arizona and 82 other locations

+33 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions High Grade B-Cell Lymphoma With MYC and BCL6 RearrangementsRecurrent Diffuse Large B-Cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell TypeRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRecurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 RearrangementsRecurrent High Grade B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.