Rituximab, Lenalidomide, and Nivolumab in Treating Participants With Relapsed or Refractory Non-Germinal Center Type Diffuse Large B Cell Lymphoma or Primary Central Nervous System Lymphoma

NCT03558750 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: VICC PCL 1758NCI-2018-01092
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of lenalidomide when given in combination with rituximab and nivolumab and how well they work in treating participants with non-germinal center type diffuse large B cell lymphoma or primary central nervous system lymphoma that has come back or isn't responding to treatment. Monoclonal antibodies, such as rituximab and nivolumab, may interfere with ability of cancer 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 rituximab, lenalidomide, and nivolumab may work better in treating participants with diffuse large B cell lymphoma.

Conditions

Recurrent Central Nervous System Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Central Nervous System Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) (Phase I)

  The maximum-tolerated dose (MTD) is the highest dose at which no more than one dose limiting toxicities are observed among 6 subjects. The MTD of lenalidomide in combination with standard doses of rituximab and nivolumab will be determined from 3+3 design.

  At the end of cycle 2 (each cycle is 28 days)

• Overall response rate (complete response, partial response, or stable disease) (Phase II)

  Parametric tests such as t-test or the non-parametric statistical methods such as Wilcoxon rank sum will be used to compare differences in the means for endpoints of interest between response and non-response groups.

  At the end of cycle 8 (each cycle is 28 days)

Secondary Outcomes (6)

• Time to progression (complete response, partial response, or stable disease)

  Up to 4 years

• Progression free survival

  From the time of enrollment in the study until progression, relapse, or death, assessed up to 4 years

• Overall survival

  From the time of enrollment in the study until death, assessed up to 4 years

• Incidence of adverse events per national Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03

  Up to 30 days after treatment

• Difference in overall response rate between those with and without programmed cell death ligand 1 (PD-L1) protein expression in tumor (subgroup analysis)

  Up to 4 years

Study Arms (1)

Treatment (nivolumab, rituximab, lenalidomide)

EXPERIMENTAL

Nivolumab give by IV over 60 minutes on days 1 and 15, rituximab IV on day 1, and lenalidomide by mouth once per day on days 1-21. Repeats every 28 days for up to of 8 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response or stable disease at the end of 8 cycles will be offered lenalidomide and nivolumab maintenance for up to 12 courses.

Biological: Nivolumab; Biological: Rituximab; Drug: Lenalidomide

Interventions

Nivolumab BIOLOGICAL

Given by IV

Treatment (nivolumab, rituximab, lenalidomide)

Rituximab BIOLOGICAL

Given by IV

Treatment (nivolumab, rituximab, lenalidomide)

Lenalidomide DRUG

Given by mouth

Treatment (nivolumab, rituximab, lenalidomide)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign an informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements in the opinion of the investigator
• Patients with histological confirmation of relapsed/refractory non-GCB type (using Hans algorithm) diffuse large B cell lymphoma (DLBCL) or relapsed/refractory primary CNS lymphoma (PCNSL) with at least one of the following characteristics:
• Definition of refractory disease: progression of disease based on Cheson criteria for DLBCL or international primary CNS lymphoma cooperative group for PCNSL either with nonresponse or progression within 3 months of prior therapy
• Definition of relapsed disease: progression of disease based on Cheson criteria for DLBCL or International primary CNS lymphoma cooperative group for PCNSL at least 3 months after prior therapy
• Definition of non-GCB subtype (Hans algorithm): cases will be subclassified based on immunohistochemical staining with CD10, BCL-6 and MUM-1 as previously described.
• Patients should have exhausted (or be ineligible for) approved therapies known to provide clinical benefit for DLBCL or PCNSL (e.g. high dose chemotherapy with autologous stem cell transplant, chimeric antigen receptor-transduced \[CAR-T\] therapy, etc.).
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry.
• Absolute neutrophil count \>= 1000/mm\^3 within 45 days prior to initiation of therapy. (Patients with documented marrow involvement (with lymphoma) or hypersplenism secondary to involvement of the spleen by lymphoma at the time of randomization are not required to meet the parameter).
• Platelet count \>= 75K /mm\^3 within 45 days prior to initiation of therapy. (Patients with documented marrow involvement (with lymphoma) or hypersplenism secondary to involvement of the spleen by lymphoma at the time of randomization are not required to meet the parameter).
• Serum creatinine =\< 2.0 mg/dL or creatinine clearance of \> 40 ml/min within 45 days prior to initiation of therapy. (Patients with documented marrow involvement (with lymphoma) or hypersplenism secondary to involvement of the spleen by lymphoma at the time of randomization are not required to meet the parameter).
• Total bilirubin =\< 1.5 mg/dL within 45 days prior to initiation of therapy. (Patients with documented marrow involvement (with lymphoma) or hypersplenism secondary to involvement of the spleen by lymphoma at the time of randomization are not required to meet the parameter).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x upper limit of normal (ULN) within 45 days prior to initiation of therapy. (Patients with documented marrow involvement (with lymphoma) or hypersplenism secondary to involvement of the spleen by lymphoma at the time of randomization are not required to meet the parameter).
• Disease free of prior malignancies for \>= 3 years with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program, and be willing and able to comply with the requirements of the Revlimid REMS program. program, and be willing and able to comply with the requirements of the Revlimid REMS program.

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent.
• Pregnant or breast feeding females (lactating females must agree not to breast feed while taking lenalidomide).
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide.
• Known prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Concurrent use of other anti-cancer agents or treatments.
• Patients with a prior history of pulmonary toxicity due to medications (Ex: history of carmustine \[BCNU\] toxicity).
• Active human immunodeficiency virus (HIV) infection or infectious hepatitis, type B or C.
• Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of hepatitis B surface antigen \[HBsAg\]) may be included if HBV deoxyribonucleic acid (DNA) is undetectable. If enrolled, patients must be willing to undergo monthly HBV DNA testing.
• HIV positive patients may enroll if they meet all of the below criteria:
• HIV is sensitive to antiretroviral therapy.
• Must be willing to take effective antiretroviral therapy if indicated.
• No history of CD4 prior to or at the time of lymphoma diagnosis \< 300 cells/mm\^3.
• No history of acquired immunodeficiency syndrome (AIDS)-defining conditions.

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Nivolumab; Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Nishitha Reddy, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: June 15, 2018
• Study Start: June 14, 2018
• Primary Completion: April 16, 2019
• Study Completion: April 16, 2019
• Last Updated: April 25, 2019

Record last verified: 2019-04

Locations

US (1)