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

NCT04120350 | Unknown Phase 1

• 1 other identifier: PUMCH-NHL-004
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Central Nervous System Lymphoma

Keywords

lenalidomide; rituximab; methorexate; Primary Central Nervous System Lymphoma; maintenance therapy

Outcome Measures

Primary Outcomes (1)

• 2 years progression-free survival

  2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up without relapsing

  From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Secondary Outcomes (2)

• 2 years overall survival

  From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years

• dose-limiting toxicity（DLT）

  from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).

Study Arms (1)

R2-MTX-LEN

EXPERIMENTAL

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.

Drug: Methotrexate; Drug: Rituximab; Drug: Lenalidomide

Interventions

Methotrexate DRUG

3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol

R2-MTX-LEN

Rituximab DRUG

375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol

R2-MTX-LEN

Lenalidomide DRUG

In phase 1b study, a 3+3 design dose- escalation will be taken. 3 levels should be tested, 15/20/25mg orally d1-14, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol. \[update 02-Jun-2020: the phase Ib trial has finished,and no MDT was obsevered in 25mg group. So the recommanded phase II dose was 25mg.\] In phase II study, 25mg daily is considered as an experiment dose for the induction cycles. In both phase Ib and II study, the does of lenalidomide maintenance is fixed to 25mg orally d1-21 every 28 days for 1 cycle. The duration of maintenance is 2 years.

R2-MTX-LEN

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Beijing Tiantan Hospital: collaborator
• Xuanwu Hospital, Beijing: collaborator
• Peking University Third Hospital: collaborator
• Beijing Hospital: collaborator
• Peking University First Hospital: collaborator
• Chinese PLA General Hospital: collaborator

Study Sites (1)

Daobin Zhou

Beijing, Dongcheng District, 100730, China

RECRUITING

MeSH Terms

Interventions

Methotrexate; Rituximab; Lenalidomide

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2019
• First Posted: October 9, 2019
• Study Start: August 16, 2019
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2024
• Last Updated: June 5, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)