Rituximab Plus Methotrexate With or Without Lenalidomide in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

Zhejiang University

Status and phase: Enrolling; Phase 2

Conditions: PCNSL

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04481815

IR2020001238

Details and patient eligibility

About

It is a multicenter, open-Label, randomised phase 2 study to compare the efficacy and safety study of R2-MTX chemotherapy（Lenalidomide, Rituximab and Methotrexate）with R-MTX chemotherapy（Rituximab and Methotrexate ）as first-line regimens in the treatment of newly diagnosed primary central nervous system lymphoma.2-year Progression free survival (PFS) is the primary endpoint.

Full description

This is a multicenter, open-Label, randomised phase 2 study designed to evaluate the efficacy and safety of rituximab plus methotrexate with or without lenalidomide as first-line regimens in the treatment of primary central nervous system lymphoma. A total of 240 patients plan to participate in this study to receive a total 6 cycles of induction chemotherapy followed by 4 cycles of maintenance chemotherapy. Follow-ups should be taken up to the first 3 years.The primary endpoints were 2-year PFS rate and and secondary endpoints including objective response rate (ORR), PFS, overall survival (OS), and adverse events.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma
2. Age range 18-75 years old.
3. Eastern Cooperative Oncology Group performance status 0 to 3.
4. Previously untreated. Patients treated with steroid alone are eligible.
5. Patient's who are not planned to undergo consolidation with autologous hematopoietic stem cell transplantation（HSCT）.
6. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI.
7. Life expectancy of ≥ 3 months (in the opinion of the investigator).
8. Participants must be able to understand and be willing to sign a written informed consent document.
9. Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 6 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 6 months after the last dose.
10. Women of childbearing potential must have a negative plasma pregnancy test upon study entry.
11. Adequate renal function: Estimated glomerular filtration rate (GFR) or estimated creatinine clearance (CrCl) ≥ 50 mL/min;Serum creatinine ≤ 2 times the upper limit of normal.
12. Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value & Bilirubin < 2 X upper normal value.
13. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL.

Exclusion criteria

1. Patient with systemic, non-CNS lymphoma metastatic to the CNS.
2. Patient is concurrently using other approved or investigational antineoplastic agents.
3. Presence of active hepatitis B virus(HBV) infection (HBsAg positive and HBV-DNA≥ 104), hepatitis C virus(HCV) infection, acquired and congenital immunodeficiency diseases include but not limited to HIV.
4. Patient is allergic to components of the study drug.
5. Patient has an active concurrent malignancy requiring active therapy.
6. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening.
7. Patient is known to have an uncontrolled active systemic infection.
8. Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
9. Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive plasma human chorionic gonadotropin(hCG) laboratory test of > 5 mIU/mL.
10. The patient is unwell or unable to participate in all required study evaluations and procedures.
11. Drug abuse, medical, psychological or social conditions which may interfering with subjects' participation in the study or evaluation of the results.
12. Patients considered unsuitable to participate in the study by the researchers.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

R2-MTX

Experimental group

Description:

Experimental arm will be treated with R2-MTX regimen(Lenalidomide plus Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved complete remission（CR）or partial remission（PR）with additional whole-brain radiotherapy（WBRT）, they processed to R2 maintenance(Lenalidomide plus Rituximab) for 4 cycles.

Treatment:

Drug: Methotrexate

Drug: Lenalidomide

Drug: Rituximab

R-MTX

Sham Comparator group

Description:

Control arm will be treated with R-MTX regimen(Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved CR or PR with additional WBRT, they processed to Lenalidomide maintenance for 4 cycles.

Treatment:

Drug: Methotrexate

Drug: Rituximab