Early Systemic Central Nervous System Prophylaxis in Diffuse Large B-cell Lymphoma

Study Overview
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Brief Summary
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Phase 2 single-institution trial of early systemic central nervous system prophylaxis in high-risk diffuse large B-cell lymphoma

Detailed Description
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This is a prospective phase 2 clinical trial of systemic central nervous system prophylaxis among patients with diffuse large B-cell lymphoma at high risk of central nervous system recurrence. The main objective is to evaluate safety and efficacy of early institution of intensive central nervous system prophylaxis in a high-risk group to minimize the risk of a devastating central nervous system recurrence. Patients receive standard primary immunochemotherapy with an addition of planned central nervous system prophylaxis courses on or around day 15 of cycles 2, 4, and 6. Growth factor support and Pneumocystis jirovecii prophylaxis is required. The primary endpoint of this pilot study is protocol-defined toxicity, whereas efficacy (cumulative incidence of central nervous system recurrence) will be a secondary endpoint.

Official Title
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Early Systemic Central Nervous System Prophylaxis in Diffuse Large B-cell Lymphoma

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosis of diffuse large B-cell lymphoma, planned first-line therapy using the standard rituximab- and anthracycline-containing regimens No central nervous system involvement on initial staging Performance status of 0 or 1 (Eastern Cooperative Oncology Group scale) Renal function: creatinine clearance >45 ml/min Not pregnant; agreeable to contraception Written informed consent High risk for central nervous system recurrence as determined by one of the following high-risk features: high central nervous system International Prognostic Index, testicular, breast, or uterine involvement, dual expresser or double/triple-hit status, HIV positive status, or Molecularly defined high-risk subtype. Exclusion Criteria: pregancy unable to provide informed consent significant comorbidity in the investigator's judgement

Ages Eligible for Study
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Minimum Age: 18 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: CNS prophylaxis protocol<br>Patients will receive central nervous system prophylaxis protocol using high-dose methotrexate and cytarabine. | Drug: Methotrexate<br>* Systemic methotrexate<br>* Other names: Methotrexate sodium;Drug: Cytarabine<br>* Systemic cytarabine<br>* Other names: Cytosar-U;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion with clinically significant toxicity | Clinically significant toxicity as defined in the protocol | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of central nervous system recurrence | Cumulative incidence of central nervous system recurrence | 2 years |