What side effects are associated with this type of intervention?

Common treatments for Diffuse Large B-Cell Lymphoma (DLBCL) that involve lenalidomide, which blocks the growth of new blood vessels necessary for tumor growth, can have several side effects. These include fatigue, cytopenias (such as neutropenia, anemia, and thrombocytopenia), gastrointestinal issues (like diarrhea and constipation), rash, and an increased risk of infections. Additionally, patients may experience more severe side effects such as deep vein thrombosis and pulmonary embolism. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Diffuse Large B-Cell Lymphoma (DLBCL), including immunomodulatory drugs like lenalidomide, which inhibits angiogenesis necessary for tumor growth. Lenalidomide is often used in combination with other agents such as rituximab, a monoclonal antibody targeting CD20 on B-cells. Additionally, CAR-T cell therapies like axicabtagene ciloleucel and tisagenlecleucel have been approved for relapsed or refractory DLBCL. These therapies harness the patient's own immune cells to target and destroy cancer cells. Other approved treatments include chemotherapy regimens like R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and targeted therapies such as polatuzumab vedotin, which delivers cytotoxic agents directly to cancer cells.

What other types of research exist?

Promising novel alternatives to Lenalidomide for Diffuse Large B-Cell Lymphoma (DLBCL) patients include: 1) CAR T-cell therapies (e.g., axicabtagene ciloleucel, tisagenlecleucel) which modify a patient's T-cells to target lymphoma cells, 2) Bispecific T-cell engagers (BiTEs) like blinatumomab that direct T-cells to attack lymphoma cells, and 3) Antibody-drug conjugates (ADCs) such as polatuzumab vedotin, which deliver cytotoxic agents directly to cancer cells. These therapies have shown promising results in clinical trials and are expected to be significant in the treatment landscape by 2024.

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Antimetabolite

Lenalidomide + Nivolumab for Lymphoma

Phase 1

Recruiting

Led By Alvaro J Alencar

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

Histologically proven primary CNS diffuse large b-cell lymphoma confirmed by one of the following: Brain biopsy or resection, Cerebrospinal fluid, Vitreous fluid

No prior organ transplantation to exclude post-transplant lymphoproliferative disorders

Must not have

No concurrent malignancy requiring active therapy

No untreated chronic hepatitis B virus (HBV) infection with detectable HBV viral load

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of drugs to treat a rare brain cancer. The treatment aims to starve the tumor, boost the immune system, and stop cancer cells from growing. It targets patients with primary CNS lymphoma who may not respond well to standard treatments.

Who is the study for?

Adults diagnosed with primary CNS diffuse large B-cell lymphoma who haven't had prior chemotherapy, radiation, or organ/stem cell transplants. They must have a certain level of physical function and adequate blood counts. Pregnant or nursing women are excluded, as well as those with autoimmune diseases that could affect the trial's safety.

What is being tested?

The trial is testing if adding Lenalidomide to Nivolumab along with usual drugs Rituximab and Methotrexate can improve treatment for primary CNS lymphoma. It aims to find the best dose and see if these drugs can extend control over the cancer after initial success.

What are the potential side effects?

Possible side effects include immune system reactions leading to inflammation in various organs, infusion-related reactions from monoclonal antibodies like Nivolumab and Rituximab, potential blood vessel growth inhibition by Lenalidomide which might affect tumor nutrition.

Eligibility Criteria

Inclusion Criteria

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

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My diagnosis of CNS lymphoma was confirmed through a biopsy or fluid test.

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I have not had an organ transplant.

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I have not had chemotherapy or radiation for lymphoma.

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I have not had a stem cell transplant from a donor.

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I am not pregnant or nursing and have a negative pregnancy test.

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I am 18 years old or older.

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My lymphoma is only in my central nervous system.

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I have never had non-Hodgkin lymphoma.

Exclusion Criteria

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

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I am not currently receiving treatment for another cancer.

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I do not have an active hepatitis B infection.

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I do not have untreated HIV or a low CD4+T-cell count.

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I do not have HIV and my brain lymphoma is related to the Epstein Barr virus.

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I cannot tolerate common blood thinners.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Maximum tolerated dose (MTD)

Proportion of evaluable patients who are able to stay on maintenance therapy

Secondary study objectives

Incidence of adverse events

Overall Survival (OS)

Overall response

+1 more

Other study objectives

Minimal residual disease (MRD)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (rituximab, methotrexate, lenalidomide, nivolumab)Experimental Treatment11 Interventions

INDUCTION: Patients receive rituximab IV on day 1, methotrexate IV over 2 hours or PO on day 2, lenalidomide PO daily on days 5-9, and nivolumab IV over 30 minutes on day 14. (In dose level IV that includes nivolumab, the doses of rituximab for cycles 2-6 may be given on the same day as nivolumab for the previous cycle). Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response, partial response, or stable disease proceed to maintenance therapy. MAINTENANCE: Within 6 weeks after the last dose of lenalidomide in induction therapy, patients receive lenalidomide PO daily on days 1-21, and nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI, CT, PET/CT, lumbar puncture, bone marrow aspirate and biopsy, testicular ultrasound and ECHO. (See Detailed Description)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Rituximab

1999

Completed Phase 4

~2990

Ultrasound Imaging

2018

Completed Phase 4

~760

Computed Tomography

2017

Completed Phase 2

~2790

Echocardiography

2013

Completed Phase 4

~11580

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Lenalidomide

2005

Completed Phase 3

~2240

Lumbar Puncture

2016

Completed Phase 3

~510

Methotrexate

2019

Completed Phase 4

~4400

Bone Marrow Aspiration and Biopsy

2016

Completed Phase 1

~40

Nivolumab

2015

Completed Phase 3

~4010

Positron Emission Tomography

2011

Completed Phase 2

~2200

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 Diffuse Large B-Cell Lymphoma (DLBCL) include chemotherapy, immunotherapy, and targeted therapies. Chemotherapy agents like R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) work by killing rapidly dividing cancer cells. Immunotherapy, such as rituximab, targets CD20 on B-cells, marking them for destruction by the immune system. Targeted therapies like lenalidomide inhibit angiogenesis, the formation of new blood vessels, which is crucial for tumor growth and survival. These mechanisms are vital for DLBCL patients as they directly attack the cancer cells, enhance the immune response against the tumor, and cut off the tumor's blood supply, thereby inhibiting its growth and spread.