R2-MTX With Lenalidomide Maintenance in Newly-diagnosed PCNSL：a Multicenter Phase Ib/II Stuty (REMLA)

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Primary Central Nervous System Lymphoma

Treatments: Drug: Lenalidomide; Drug: Methotrexate; Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT04120350

PUMCH-NHL-004

Details and patient eligibility

About

This is a multicenter prospective single arm phase Ib/II study, and the purpose of this study is to evaluate the safety and efficiency of R2-MTX regimen (rituximab & lenalidomide & methotrexate) combined with lenalidomide maintenance in newly-diagnosed primary central nervous system lymphoma. 2-year Progression free survival (PFS) of the cohort is the primary endpoint.

Full description

There are 2 section of this trial. Step1 is a phase Ib study.The patients will be treated with R2-MTX regimen （Rituximab 375mg/m2 IV d0, methotrexate 3.5g/m2 civ d1, lenalidomide 15-25mg d1-14, 21 days per cycle) as induction regimen.The dose of rituximab and methotrexate is fixed dose. This is a 3+3 design Ib phase dose-escalation study to determined the maximum tolerated dose(MTD) of lenalidomide dose in combined regimen. 3 levels of lenalidomide dose will be investigated, 15mg, 20mg and 25mg. If the DLT is not found, the dose of 25mg qd will be used for phase II trial.

[update 02-Jun-2020：the recommended phase II doses is 25mg d1-14]

Step 2 is a single-arm phase 2 study with fixed does of R2-MTX regimen in newly-diagnosed PCNSL patients. The response will be evaluated every 2 cycles. Patients who achieved complete remission (CR) or partial remission (PR) will receive further treatment, and there are 6 cycles of R2-MTX regimen for the induction. The patients with stable disease (SD) or progressed disease (PD) will withdraw from the trial and receive salvage regimens. After total 6 induction cycles, the investigators evaluate the efficiency again, the patients with CR or PR will go to lenalidomide maintenance for 2 years or until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. And the patients with SD or PD will receive salvage regimen.

[update 02-Jun-2020：Younger patients(≤60 years) who achieve PR after 6 cycles of induction therapy will be candidates of high-dose chemotherapy and stem cell rescue. Lenalidomide maintenance will be administed after the high-dose chemotherapy. Older patients(>60 years) who achieve PR after 6 cycles of induction will go to lenalidomide maintenance directly.] During following-up, surveillance examination and brain magnetic resonance imaging (MRI) scans can be performed every 3 months up to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease relapses.

Enrollment: 47 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Newly-diagnosed primary vitreoretinal lymphoma
• ECOG≤2
• creatinine clearance rate (CCR) ≥ 50ml/h, according to Cockcroft-Gault
• Total bilirubin < 2 upper limits of normal, alanine aminotransferase（ALT） < 3 upper limits of normal
• HIV-Ab negative
• Sign the Informed consent
• Women of childbearing potential must understand that the study medication could have a potential teratogenic risk. They should undergo complete contraception during the study period.
• Male subjects must agree to use condoms throughout study drug therapy.

Exclusion criteria

• Pre-existing uncontrolled active infection
• Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria
• systemic lymphoma involved CNS
• Pregnancy or active lactation
• Co-existing tumors

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 1 patient group

R2-MTX-LEN

Experimental group

Description:

Phase Ib：Experimental arm will be treated with R2-MTX regimen for 6 cycles as initiate induction, the dose of lenalidomide was escalated from 15mg， 20mg， 25mg to test DLT by 3+3 design, meanwhile the dose of rituximab and methotrexate is fixed. If the patients achieved CR or PR by MRI and CSF evaluation, they processed to lenalidomide maintenance for 2 years. Phase II: the patients will be treated by fixed dose of R2-MTX regimen (established lenalidomide dose from phase Ib study) for 6 cycles. the efficiency evaluation will be performed every 2 cycles, the patients who achieved CR or PR will finish the total 6 cycles of induction therapy, then begin the stage of lenalidomide maintenance for 2 years. Follow-ups should be taken for 5 years.

Treatment:

Drug: Lenalidomide

Drug: Rituximab

Drug: Methotrexate