NCT04609046|RecruitingPhase 1FDA Drug

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

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

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2020-08331A051901U10CA180821

Study Type

interventional

Target

Locations

1 country

Sites

Timeline

RegisteredOct 2020

StartedMay 2021

CompletionApr 2027

Brief Summary

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).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1

Timeline

9mo left

Started May 2021

Longer than P75 for phase_1

Geographic Reach

1 country

54 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.9 years study duration

Study Progress86%

May 2021Apr 2027

First Submitted

Initial submission to the registry

October 29, 2020

Completed

1 day until next milestone

First Posted

Study publicly available on registry

October 30, 2020

Completed

7 months until next milestone

Study Start

First participant enrolled

May 24, 2021

Completed

5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Last Updated

June 3, 2026

Status Verified

April 1, 2026

Enrollment Period

5.9 years

First QC Date

October 29, 2020

Last Update Submit

June 2, 2026

Conditions

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

Outcome Measures

Primary Outcomes (2)

Maximum tolerated dose
Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients). The number and severity of all adverse events will be tabulated and summarized in this patient population both overall and by dose level according to the Common Terminology Criteria for Adverse Events (CTCAE) Cancer Therapy Evaluation Program version 5.0 criteria. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group.
During the first 14-day cycle of treatment
Proportion of evaluable patients who are able to stay on maintenance therapy
The proportion of evaluable patients who meet the criteria for maintenance feasibility, along with the 95% exact binomial confidence interval, will be provided.
Up to 6 months

Secondary Outcomes (4)

Overall response
Up to 5 years
Progression free survival (PFS)
Time from start of induction treatment to progression or death due to any cause
Overall Survival (OS)
Time from start of induction treatment to death due to any cause
Incidence of adverse events
Up to 5 years

Other Outcomes (1)

Minimal residual disease (MRD)
Up to 5 years

Study Arms (1)

Treatment (rituximab, methotrexate, lenalidomide, nivolumab)

EXPERIMENTAL

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)

Procedure: Bone Marrow Aspiration and BiopsyProcedure: Computed TomographyProcedure: Echocardiography TestDrug: LenalidomideProcedure: Lumbar PunctureProcedure: Magnetic Resonance ImagingDrug: MethotrexateBiological: NivolumabProcedure: Positron Emission TomographyBiological: RituximabProcedure: Ultrasound Imaging