RECRUITING

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

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

Phase I Trial of Methotrexate, Rituximab, Lenalidomide, and Nivolumab (Nivo-MR2) Induction Followed by Lenalidomide and Nivolumab Maintenance in Primary CNS Lymphoma

Quick Facts

Study Start:2021-05-24

Study Completion:2025-05-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04609046

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion 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

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Alvaro J Alencar

PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Study Locations (Sites)

Cedars Sinai Medical Center

Los Angeles, California, 90048

United States

UCSF Medical Center-Parnassus

San Francisco, California, 94143

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324

United States

Iowa Methodist Medical Center

Des Moines, Iowa, 50309

United States

Mission Cancer and Blood - Des Moines

Des Moines, Iowa, 50309

United States

Broadlawns Medical Center

Des Moines, Iowa, 50314

United States

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314

United States

Iowa Lutheran Hospital

Des Moines, Iowa, 50316

United States

Trinity Regional Medical Center

Fort Dodge, Iowa, 50501

United States

Methodist West Hospital

West Des Moines, Iowa, 50266-7700

United States

Maine Medical Center-Bramhall Campus

Portland, Maine, 04102

United States

Maine Medical Center- Scarborough Campus

Scarborough, Maine, 04074

United States

Maine Medical Partners - South Portland

South Portland, Maine, 04106

United States

Hickman Cancer Center

Adrian, Michigan, 49221

United States

Toledo Clinic Cancer Centers-Monroe

Monroe, Michigan, 48162

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Siteman Cancer Center-South County

Saint Louis, Missouri, 63129

United States

Siteman Cancer Center at Christian Hospital

Saint Louis, Missouri, 63136

United States

Siteman Cancer Center at Saint Peters Hospital

Saint Peters, Missouri, 63376

United States

Overlook Hospital

Summit, New Jersey, 07902

United States

Northwell Health/Center for Advanced Medicine

Lake Success, New York, 11042

United States

North Shore University Hospital

Manhasset, New York, 11030

United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032

United States

NYP/Weill Cornell Medical Center

New York, New York, 10065

United States

State University of New York Upstate Medical University

Syracuse, New York, 13210

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

United States

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, 43623

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

Rhode Island Hospital

Providence, Rhode Island, 02903

United States

Medical University of South Carolina

Charleston, South Carolina, 29425

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

West Virginia University Healthcare

Morgantown, West Virginia, 26506

United States

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, 54701

United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601

United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449

United States

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, 54548

United States

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, 54868

United States

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, 54482

United States

Marshfield Medical Center - Weston

Weston, Wisconsin, 54476

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Alvaro J Alencar, PRINCIPAL_INVESTIGATOR, Alliance for Clinical Trials in Oncology

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-24

Study Completion Date2025-05-31

Study Record Updates

Study Start Date2021-05-24

Study Completion Date2025-05-31

Terms related to this study

Additional Relevant MeSH Terms

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