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

Primary Central Nervous System Lymphoma Clinical Trial

— REMLA  

Official title:

R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04120350
• Other study ID #: PUMCH-NHL-004
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 16, 2019
• Est. completion date: August 2024

Study information

• Verified date: June 2020
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 47
• Est. completion date: August 2024
• Est. primary completion date: August 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

Drug:
• Methotrexate
3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
• Rituximab
375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
• Lenalidomide
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.

Locations

Country	Name	City	State
China	Daobin Zhou	Beijing	Dongcheng District

Sponsors (7)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital	Beijing Hospital, Beijing Tiantan Hospital, Chinese PLA General Hospital, Peking University First Hospital, Peking University Third Hospital, Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years overall survival	2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up alive	From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
Secondary	dose-limiting toxicity(DLT)	all treatment-related, critically relevant grade 3/4 adverse event (AE) that occured in the first 21 days after the start of the first treatment.	from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).