- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04120350
R2-MTX With Lenalidomide Maintenance in Newly-diagnosed PCNSL:a Multicenter Phase Ib/II Stuty (REMLA)
R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Dongcheng District
-
Beijing, Dongcheng District, China, 100730
- Recruiting
- Daobin Zhou
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: R2-MTX-LEN
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. |
3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle.
6 cycles will be prescribed as protocol
375mg/m2 intravenous infusion d1, every 21 days for 1 cycle.
6 cycles will be prescribed as protocol
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
2 years progression-free survival
Time Frame: 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
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
2 years overall survival
Time Frame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
|
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
|
dose-limiting toxicity(DLT)
Time Frame: from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).
|
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).
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Lenalidomide
- Rituximab
- Methotrexate
Other Study ID Numbers
- PUMCH-NHL-004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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