Rituximab, Lenalidomide Combined With Methotrexate and Temozolomide For Primary Central Nervous System Lymphoma

Study Overview
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Brief Summary
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This is a prospective single arm, multi-center, phase II clinical trial to observe the efficacy and safety of Rituximab, Lenalidomide combined with high-dose Methotrexate and Temozolomide (RL-MT) in the first-line treatment for patients with primary central nervous system lymphoma.

Official Title
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A Single Arm, Multi-center, Phase II Clinical Trial of Rituximab, Lenalidomide Combined With High-dose Methotrexate and Temozolomide (RL-MT) in the First-line Treatment for Patients With Primary Central Nervous System Lymphoma

Conditions
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Primary Central Nervous System Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Lenalidomide
* Drug: Methotrexate
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 to 70 years old (including 18 and 70) Diagnosed as primary central nervous system lymphoma (limited to the brain, spinal cord, meninges and eyeballs, without involvement of other parts) Having not received anti-tumor therapy before enrollment (except for tumor resection and biopsy and the use of glucocorticoids to reduce central nervous system symptoms) Having at least one measurable lesions World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 ( ECOG 3 due to tumors can be included after being fully assessed by the investigator) Life expectancy no less than 1 month enough main organ function Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study Agreeing to sign the written informed consents Exclusion Criteria: Diagnosed as secondary central nervous system lymphoma Diagnosed as CD20 negative large B cell primary central nervous system lymphoma Active malignant tumor need be treated at the same time Other malignant tumor history Serious surgery and trauma less than two weeks Patients with active tuberculosis Systemic therapy for serious acute/chronic infection Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months HIV-positive, AIDS patients and untreated active hepatitis Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months Patients with a history of mental illness or drug abuse Poor compliance during the trial and/or follow-up phase Allergies or people who are known to be allergic to any active ingredients, excipients, mouse-derived products or heterologous protein contained in this trial Researchers determine unsuited to participate in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RL-MT<br>Induction Chemotherapy: Rituximab, 375mg/m2, Intravenous administration on day 0, Lenalidomide, 25mg oral administration on day 1 to 10, combined with regimen: Methotrexate, 3mg/m2, Intravenous administration (pumping for 3h) on day 1 of each 3-week cycle, Temozolomide, 150mg/m2/d oral administration on day 1 to 10. Consolidation Treatment: Autologous hematopoietic stem cell transplantation or reduced whole brain radiotherapy after high-dose chemotherapy. Maintenance Treatment: Lenalidomide, 10mg oral administration on day 1 to 21 of each 4-week cycle for 12 months. | Drug: Rituximab<br>* Induction Chemotherapy: 375mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression/stable disease or unacceptable toxicity develops, up to 6 cycles.<br>* Other names: RiTUXimab Injection;Drug: Lenalidomide<br>* Induction Chemotherapy: 25mg, oral administration on day 1 to 10 of each 3-week cycle until disease progression/stable disease or unacceptable toxicity develops, up to 6 cycles. Maintenance Treatment: 10mg oral administration on day 1 to 21 repeated every 4 weeks until disease progression or unacceptable toxicity develops, up to 12 cycles.<br>* Other names: Lenalidomide capsule;Drug: Methotrexate<br>* Induction Chemotherapy: 3mg/m2, Intravenous administration (pumping for 3h) on day 1 of each 3-week cycle until disease progression/stable disease or unacceptable toxicity develops, up to 6 cycles.<br>* Other names: Methotrexate Injectable Solution;Drug: Temozolomide<br>* Induction Chemotherapy: 150mg/m2/d oral administration on day 1 to 10 of each 3-week cycle until disease progression/stable disease or unacceptable toxicity develops, up to 6 cycles.<br>* Other names: Temozolomide capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year progression-free survival | the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first | from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | the total proportion of patients with complete response (CR) and partial response (PR) | every 6 weeks from the day of the first cycle of induction chemotherapy treatment and every 8 weeks from the day of the first cycle of maintenance treatment to 18 months after last patient's enrollment (each cycle is 21 days) | 
| overall survival | from date of first day of treatment to the date of death by any cause | from date of the first cycle of treatment to the date of death from any cause, assessed up to 5 years (each cycle is 21 days) | 
| incidence and relationship with study drugs of grade 3-4 adverse events | the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03) | from the date of the first cycle of treatment to 18 months after last patient's enrollment (each cycle is 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Central Nervous System Lymphoma, RL-MT