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
2 other identifiers
interventional
53
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jul 2015
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2015
CompletedFirst Posted
Study publicly available on registry
May 18, 2015
CompletedStudy Start
First participant enrolled
July 31, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2025
CompletedResults Posted
Study results publicly available
February 27, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2026
CompletedMarch 9, 2026
March 1, 2026
9.7 years
May 13, 2015
February 9, 2026
March 5, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (Complete + Partial Responses)
To determine the overall response rate (ORR) in subjects with relapsed follicular lymphoma (FL) treated with Rituximab plus pembrolizumab therapy. II. To determine the ORR in subjects with relapsed/refractory FL and relapsed/refractory diffuse large B-Cell lymphoma (DLBCL) who failed chimeric antigen receptor (CAR) T cell therapy and rea treated with rituximab in combination with pembrolizumab and lenalidomide (Cohort 2)
Approximately 1 year and 6 months
Secondary Outcomes (4)
Incidence of Toxicity
Up to 30 days after the completion of study treatment
Complete Response Rate
Up to 2 years after completion of study treatment
Progression-free Survival (PFS)
Up to 2 years after completion of study treatment
Overall Survival
Up to 2 years after completion of study treatment
Study Arms (2)
Cohort I (rituximab, pembrolizumab)
EXPERIMENTALPatients receive rituximab 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 (rituximab, pembrolizumab, lenalidomide)
EXPERIMENTALPatients 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 PO on days 1-14 every 3 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Correlative studies
Given PO
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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
- Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN, performed within 28 days of treatment initiation
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with lymphoma in the liver, performed within 28 days of treatment initiation
- International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants performed within 28 days of treatment initiation
- Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, performed within 28 days of treatment initiation
- Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- +4 more criteria
You may not qualify if:
- 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
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
- Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti- cluster of differentiation (CD)137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- Note: Subjects that received prior therapy with pidilizumab are an exception to this criterion and may qualify for the study
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Nastoupil LJ, Chin CK, Westin JR, Fowler NH, Samaniego F, Cheng X, Ma MCJ, Wang Z, Chu F, Dsouza L, Obi C, Mims J, Feng L, Zhou S, Green M, Davis RE, Neelapu SS. Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma. Blood Adv. 2022 Feb 22;6(4):1143-1151. doi: 10.1182/bloodadvances.2021006240.
PMID: 35015819DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Ranjit Nair, MD
- Organization
- The University of Texas MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Ranjit Nair
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2015
First Posted
May 18, 2015
Study Start
July 31, 2015
Primary Completion
March 31, 2025
Study Completion
April 30, 2026
Last Updated
March 9, 2026
Results First Posted
February 27, 2026
Record last verified: 2026-03