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Testing the Addition of Lenal...

Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-24

Study Completion Date

2026-05-31

Brief Summary

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This phase I trial tests the safety, side effects, best dose and effectiveness of lenalidomide when added to nivolumab and the usual drugs (rituximab and methotrexate) in patients with primary central nervous system (CNS) lymphoma. Lenalidomide may stop or slow primary CNS lymphoma by blocking the growth of new blood vessels necessary for tumor growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Methotrexate is frequently combined with other chemotherapy agents to improve response. This study may help increase the understanding of lenalidomide and nivolumab use in primary CNS lymphoma treatment. In addition, it may help researchers see whether the control of CNS lymphoma can be extended by using these study drugs as maintenance (prolonged therapy) after control is achieved with the initial chemotherapy regimen (induction).

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Detailed Description

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PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of lenalidomide when given in combination with high dose-methotrexate (HD-MTX) and rituximab, with or without nivolumab, as induction treatment of primary CNS lymphoma.

II. Determine the proportion of patients who are able to stay on maintenance therapy with lenalidomide and/or nivolumab for 6 months after induction treatment of primary CNS lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) of the combination of methotrexate, rituximab, lenalidomide, nivolumab.

II. To evaluate the effect of the treatment regimen and lenalidomide / nivolumab maintenance on progression free survival (PFS).

III. To evaluate the effect of the treatment regimen and lenalidomide / nivolumab maintenance on overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To analyze tumor tissue and cerebrospinal fluid (CSF) for gene expression profiles, and to correlate these profiles with treatment outcomes.

II. To determine whether CSF proteome and metabolome are predictors of outcomes (prognostic marker).

III. To assess response to therapy and minimal residual disease via MRI-based metrics and minimal residual disease of blood and CSF.

IV. To evaluate the relationship between neurocognitive deficits and tumor and brain volumetrics, as assessed by magnetic resonance imaging (MRI) and tumor metabolism.

OUTLINE: This is a dose-escalation study of lenalidomide.

INDUCTION: Patients receive rituximab intravenously (IV) on day 1, methotrexate IV over 2 hours or orally (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 magnetic resonance imaging (MRI) throughout the trial, computed tomography (CT) and positron emission tomography (PET)/CT during screening, and lumbar puncture at the end of the 6th cycle of induction, and after 6 months of maintenance. Patients may also undergo bone marrow aspirate and biopsy, testicular ultrasound and/or echocardiogram (ECHO) during screening.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for up to 2 years.

Conditions

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Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System

Study Design

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Allocation Method

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (rituximab, methotrexate, lenalidomide, nivolumab)

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)

Group Type EXPERIMENTAL

Bone Marrow Aspiration and Biopsy

Intervention Type PROCEDURE

Undergo bone marrow aspirate and biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT and PET/CT

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Lenalidomide

Intervention Type DRUG

Given PO

Lumbar Puncture

Intervention Type PROCEDURE

Undergo lumbar puncture

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Methotrexate

Intervention Type DRUG

Given IV or PO

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Rituximab

Intervention Type BIOLOGICAL

Given IV

Ultrasound Imaging

Intervention Type PROCEDURE

Undergo testicular ultrasound

Interventions

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Bone Marrow Aspiration and Biopsy

Undergo bone marrow aspirate and biopsy

Intervention Type PROCEDURE

Computed Tomography

Undergo CT and PET/CT

Intervention Type PROCEDURE

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Lenalidomide

Given PO

Intervention Type DRUG

Lumbar Puncture

Undergo lumbar puncture

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Methotrexate

Given IV or PO

Intervention Type DRUG

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Rituximab

Given IV

Intervention Type BIOLOGICAL

Ultrasound Imaging

Undergo testicular ultrasound

Intervention Type PROCEDURE

Other Intervention Names

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PF 05280586 PF-05280586 PF05280586 Riabni Ritemvia Rituxan Rituximab ABBS Rituximab ARRX Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography EC Echocardiography CC 5013 CC-5013 CC5013 CDC 501 Revlimid LP Spinal Tap Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Jylamvo Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039 ABP 206 BCD-263 BMS 936558 BMS-936558 BMS936558 CMAB819 MDX 1106 MDX-1106 MDX1106 NIVO Nivolumab Biosimilar ABP 206 Nivolumab Biosimilar BCD-263 Nivolumab Biosimilar CMAB819 ONO 4538 ONO-4538 ONO4538 Opdivo Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT ABP 798 ABP-798 ABP798 BI 695500 BI-695500 BI695500 Blitzima C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT P10 CT-P10 CTP10 GP 2013 GP-2013 GP2013 IDEC 102 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody IDEC102 Ikgdar Mabtas MabThera Monoclonal Antibody IDEC-C2B8 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar GP2013 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 Rituximab PVVR Rituximab-abbs Rituximab-arrx Rituximab-blit Rituximab-pvvr Rituximab-rite Rituximab-rixa Rituximab-rixi Rixathon Riximyo RTXM 83 RTXM-83 RTXM83 Ruxience Truxima 2-Dimensional Grayscale Ultrasound Imaging 2-Dimensional Ultrasound Imaging 2D-US Ultrasonography Ultrasound Ultrasound Test Ultrasound, Medical US

Eligibility Criteria

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Inclusion Criteria

* 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
* No prior chemotherapy or radiation therapy for lymphoma
* No prior allogeneic stem cell transplantation
* Use of systemic corticosteroids (dexamethasone up to 24 mg/day or equivalent) for disease control or improvement of performance status to be tapered as fast as clinically safe after initiation of therapy is permissible
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, female of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) =\< 7 days prior to registration
* Age \>= 18 years
* Karnofsky performance scale (KPS) \>= 40 (\>= 50 for patients older than 60 unless related to lymphoma on investigator's opinion)
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Calculated creatinine clearance \>= 50 mL/min by Cockcroft-Gault formula
* Total Bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
* No evidence of non-Hodgkin's lymphoma (NHL) outside CNS
* No prior history of NHL
* No history of autoimmune disorder. Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as Systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (except short course of systemic corticosteroids for disease control or improvement of performance status or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
* Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study
* No prior or concurrent malignancies with exception of surgically cured carcinoma in situ (CIS) of the uterus, carcinoma of the skin without evidence of disease for \>= 5 years
* No concurrent malignancy requiring active therapy
* No untreated hepatitis C virus (HCV) infection with detectable HCV viral load
* No untreated chronic hepatitis B virus (HBV) infection with detectable HBV viral load
* No untreated human immunodeficiency virus (HIV) infection or with detectable viral load or with CD4+T-cell count of less than 500/mm\^3
* No history of HIV infection and evidence of Epstein Barr virus (EBV)-related primary central nervous system lymphoma (PCNSL)
* Inability to tolerate anticoagulation with acetylsalicylic acid, warfarin, or direct oral anticoagulants
* No other investigational agent
* No history of severe hypersensitivity reaction to any monoclonal antibody
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to or other agents used in study
* Sulfonamide drugs, trimethoprim, salicylates, nonsteroidal anti-inflammatory drugs, penicillin, vitamin C, ciprofloxacin, and proton pump inhibitors should be held at least 48 hours prior to methotrexate administration

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alvaro J Alencar

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Site Status RECRUITING

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

North Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status RECRUITING

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, United States

Site Status RECRUITING

Saint Anthony Regional Hospital

Carroll, Iowa, United States

Site Status RECRUITING