What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, such as those in the ViPOR trial, have various side effects. Venetoclax, a BCL-2 inhibitor, can cause neutropenia, infections, and tumor lysis syndrome. Ibrutinib, a Bruton's tyrosine kinase inhibitor, is associated with diarrhea, peripheral edema, atrial fibrillation, and hypertension. Prednisone, a corticosteroid, can lead to weight gain, hyperglycemia, and increased risk of infections. Obinutuzumab, targeting CD20, may cause infusion-related reactions and neutropenia. Lenalidomide, an immune modulator, can result in neutropenia, thrombocytopenia, and an increased risk of thromboembolic events.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Non-Hodgkin's Lymphoma (NHL) that are similar to those in the ViPOR regimen. Venetoclax, a BCL-2 inhibitor, is approved for certain types of NHL, including chronic lymphocytic leukemia (CLL). Ibrutinib, a Bruton's tyrosine kinase inhibitor, is approved for various B-cell malignancies, including mantle cell lymphoma and CLL. Prednisone, a corticosteroid, is commonly used in combination chemotherapy regimens for NHL. Obinutuzumab, an anti-CD20 monoclonal antibody, is approved for use in combination with chemotherapy for follicular lymphoma and CLL. Lenalidomide, an immunomodulatory drug with anti-angiogenic properties, is approved for mantle cell lymphoma and other hematologic malignancies. These drugs target specific pathways and mechanisms involved in the pathogenesis of NHL, offering multiple therapeutic options.

What other types of research exist?

Promising novel alternatives to ViPOR for Non-Hodgkin's Lymphoma patients include: 1) Bispecific antibodies targeting CD3 and CD20 or other relevant antigens, which facilitate immune-mediated tumor cell killing. 2) CAR-T cell therapies engineered to target specific antigens on lymphoma cells, offering personalized and potent anti-tumor activity. 3) Novel agents targeting cereblon (CELMoDs), such as iberdomide, which modulate the immune system and have shown efficacy in hematologic malignancies. These alternatives leverage advanced immunotherapy and targeted therapy approaches, potentially offering improved outcomes for NHL patients.

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BTK Inhibitor

ViPOR for Lymphoma

Phase 1 & 2

Recruiting

Led By Christopher J Melani, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have histologically or cytologically confirmed B-cell lymphoma confirmed by the Laboratory of Pathology, NCI

Patients with aggressive B-cell lymphoma must have DLBCL and subtypes, transformed lymphoma, Burkitt lymphoma, as well as High-grade B-cell lymphoma with MYC and/or BCL2 and/or BCL6 rearrangement(s)

Must not have

History of other active malignancy that could affect compliance with the protocol or interpretation of results

Patients with recent chemotherapy, external beam radiation therapy, or anti-cancer antibodies

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from the date of from initial diagnosis until death from any cause; assessed every 3-6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of five drugs (ViPOR) to treat adults with B-cell lymphoma that has come back or not responded to other treatments. The drugs work together to block cancer cell survival mechanisms. One of the drugs, Venetoclax, is already used for another type of blood cancer and is being studied for its effectiveness in this treatment. The study aims to find the safest dose and see how well the treatment works.

Who is the study for?

Adults over 18 with B-cell lymphoma that has come back or hasn't improved after treatment can join. They must have had at least one prior regimen including an anti-CD20 antibody and be in good enough health to participate. Women who can bear children and men must agree to use contraception, and all participants need counseling on lenalidomide risks regularly.

What is being tested?

The ViPOR combination (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) is being tested for safety in treating B-cell lymphomas. Participants will receive these drugs in cycles of 21 days up to six times, with close monitoring especially after the first dose of venetoclax.

What are the potential side effects?

Possible side effects include reactions from IV drug administration, digestive issues due to oral medications, blood disorders from bone marrow impact, increased risk of infections due to immune system suppression by the drugs used in this trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lymphoma is confirmed to be of B-cell type by a pathology lab.

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My lymphoma is an aggressive type, such as DLBCL, Burkitt, or high-grade with specific gene rearrangements.

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I do not have active CNS lymphoma.

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I can take care of myself and perform daily activities.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have another active cancer that could interfere with the study.

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I have recently undergone chemotherapy, radiation, or received cancer-fighting antibodies.

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I have a significant history of liver problems, including hepatitis, alcohol abuse, or cirrhosis.

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I cannot take medicine by mouth due to a digestive condition.

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I have not had major surgery in the last 6 weeks.

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I have been treated with more than one of the drugs being studied before.

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I had a stem cell transplant less than 6 months ago or I have signs of graft-versus-host disease.

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I need to take warfarin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from the date of from initial diagnosis until death from any cause; assessed every 3-6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from the date of from initial diagnosis until death from any cause; assessed every 3-6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from the date of from initial diagnosis until death from any cause; assessed every 3-6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number and grade of adverse events

Secondary study objectives

Overall response rate (ORR)

Overall survival (OS)

Progression-free survival (PFS)

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

SARS-CoV-2 test positive

11%

Sepsis

11%

Abdominal pain

11%

Pneumonia

11%

Rhinovirus infection

11%

COVID-19

11%

Gastroenteritis

11%

Pneumonia pseudomonal

11%

Electrocardiogram QT prolonged

11%

Anaemia

11%

Neutrophil count decreased

11%

Hypokalaemia

11%

Febrile neutropenia

11%

Supraventricular tachycardia

11%

Blood creatinine increased

11%

White blood cell count decreased

11%

Dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm 4: Dose ExpansionExperimental Treatment5 Interventions

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

Group II: Arm 3: Dose ExpansionExperimental Treatment5 Interventions

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Group III: Arm 2: Dose EscalationExperimental Treatment5 Interventions

ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 1-6

Group IV: Arm 1: Dose EscalationExperimental Treatment5 Interventions

iPOR (ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycle 1; followed by ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, lenalidomide) for cycles 2-6

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Revlimid (lenalidomide)

2007

Completed Phase 2

~160

Prednisone

2014

Completed Phase 4

~2500

Ibrutinib

2014

Completed Phase 4

~2060

Obinutuzumab

2014

Completed Phase 3

~3470

Venetoclax

2019

Completed Phase 3

~2240

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include venetoclax, which inhibits the BCL-2 protein to promote cancer cell apoptosis; ibrutinib, which inhibits Bruton's tyrosine kinase (BTK) to disrupt B-cell receptor signaling and reduce cancer cell survival; prednisone, a corticosteroid that reduces inflammation and suppresses the immune response; obinutuzumab, a monoclonal antibody targeting CD20 on B-cells to induce cell death; and lenalidomide, which modulates the immune system and has anti-angiogenic properties to inhibit tumor growth. These mechanisms are vital for NHL patients as they offer targeted approaches to eliminate cancer cells, improve treatment efficacy, and manage disease progression.