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Rituximab and Pembrolizumab With or Without Lenalidomide in Treating Patients With Relapsed Follicular Lymphoma and Diffuse Large B-Cell Lymphoma | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE2

Rituximab and Pembrolizumab With or Without Lenalidomide in Treating Patients With Relapsed Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

Phase II Study of Rituximab Plus Pembrolizumab (MK-3475) in Subjects With Relapsed Follicular Lymphoma

NCT02446457•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase II trial studies how well rituximab and pembrolizumab with or without lenalidomide works in treating patients with follicular lymphoma and diffuse large B-cell lymphoma that has returned after a period of improvement. Immunotherapy with monoclonal antibodies, such as rituximab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rutuximab with pembrolizumab and lenalidomide may work better at treating follicular lymphoma and diffuse large B-cell lymphoma.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) in subjects with relapsed follicular lymphoma (FL) treated with rituximab plus pembrolizumab. II. To determine the ORR in subjects with relapsed/refractory FL and relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who have failed chimeric antigen receptor (CAR) T cell therapy and are treated with rituximab in combination with pembrolizumab and lenalidomide. (Cohort 2) SECONDARY OBJECTIVES: I. To determine the safety and toxicity. II. To determine the complete response rate (CRR). III. To determine the overall progression-free survival (PFS). IV. To compare PFS between patients relapsing =\< one year vs \> one year after last prior therapy. V. To determine the overall survival (OS). VI. To determine the safety and toxicity. (Cohort 2) VII. To determine the CRR. (Cohort 2) VIII. To determine the overall PFS. (Cohort 2) IX. To compare PFS between patients relapsing =\< one year vs \> one year after last prior therapy. (Cohort 2) X. To determine the OS. (Cohort 2) EXPLORATORY OBJECTIVES: I. To determine effects of rituximab plus pembrolizumab therapy on peripheral blood T cells. II. To correlate features of peripheral blood T cells with toxicities after rituximab plus pembrolizumab therapy. III. To correlate features of peripheral blood T cells with response and PFS after rituximab plus pembrolizumab therapy. IV. To correlate baseline tumor characteristics with response and PFS after rituximab plus pembrolizumab therapy. V. To determine effects of rituximab, pembrolizumab, and lenalidomide therapy on peripheral blood T cells. (Cohort 2) VI. To correlate features of peripheral blood T cells with toxicities after rituximab, pembrolizumab, and lenalidomide therapy. (Cohort 2) VII. To correlate features of peripheral blood T cells with response and PFS after rituximab, pembrolizumab, and lenalidomide therapy. (Cohort 2) VIII. To correlate baseline tumor characteristics with response and PFS after rituximab, pembrolizumab, and lenalidomide therapy. (Cohort 2) OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I: Patients receive rituximab intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22. Patients also receive pembrolizumab IV over 1 hour on day 2 every 3 weeks for up to 16 cycles (1 year) in the absence of disease progression or unacceptable toxicity. COHORT II: Patients receive rituximab IV over 4-8 hours on days 1, 8 and 15 of cycle 1, and day 1 of cycle 2. Patients also receive pembrolizumab IV over 1 hour on day 2 every 3 weeks for up to 2 years, and lenalidomide orally (PO) on days 1-14 every 3 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months thereafter.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•For cohort 1: Male or female subjects with histologic proof of follicular lymphoma grade 1, 2, or 3a relapsing after at least one prior systemic therapy that included rituximab (or other monoclonal CD20 antibody); patients should have documented rituximab-sensitive disease defined as a documented complete or partial response lasting at least 6 months after the last rituximab-containing therapy
•For cohort 2: Male or female subjects with histologic proof of follicular lymphoma grade 1, 2, or 3a relapsing after at least two prior systemic therapies, which must include CAR T cell therapy or histologic proof of DLBCL relapsing after at least two prior systemic therapies, which must include CAR T cell therapy
•Either the subject or his/her legally authorized representative be willing and able to provide written informed consent for the trial
•Have measurable disease (\>= 1.5 cm in the longest diameter for nodal or extranodal disease)
•Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
•Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L, performed within 28 days of treatment initiation
•Platelets \>= 50 x 10\^9/L, performed within 28 days of treatment initiation
•Hemoglobin \>= 8.0 g/dL, performed within 28 days of treatment initiation
•Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min GFR or CrCl for subjects with creatinine levels \> 1.5 x institutional ULN, performed within 28 days of treatment initiation
•* Creatinine clearance will be calculated per institutional standard
+9 more criteria

Exclusion Criteria

•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study drug or using an investigation device within 4 weeks of the first dose of treatment
•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
•Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events (AEs) due to agents administered more than 4 weeks earlier
•Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from AEs due to a previously administered agent; \* Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
•* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
•Has a known additional malignancy that is progressing and requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
•Has known active central nervous system (CNS) lymphoma and/or lymphomatous meningitis; subjects with previously treated CNS lymphoma and/or lymphomatous meningitis may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
•No active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators, local steroid injections or inhaled or topical steroids would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
•Has evidence of interstitial lung disease or active, non-infectious pneumonitis that required steroids or current pneumonitis
•Has an active infection requiring systemic therapy
+8 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

July 31, 2015

Primary Completion Date

March 31, 2025

Completion Date

April 30, 2026

Last Updated

March 9, 2026

Enrollment

ACTUAL participants

Conditions

Recurrent Diffuse Large B-Cell LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3a Follicular Lymphoma

Interventions

Laboratory Biomarker Analysis

OTHER

Lenalidomide

DRUG

Pembrolizumab

BIOLOGICAL

Rituximab

BIOLOGICAL

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RECRUITINGPHASE2

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 9, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Rituximab and Pembrolizumab With or Without Lenalidomide in Treating Patients With Relapsed Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

Inclusion Criteria

Exclusion Criteria

Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma

Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Epcoritamab Plus Standard of Care Platinum-Based Chemotherapy and Autologous Hematopoietic Cell Transplant for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

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Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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