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

Phase 2

Withdrawn

• Conditions: Diffuse Large B Cell Lymphoma
• Interventions: Drug: Methotrexate; Drug: Cytarabine

• Registration Number: NCT03719560
• Lead Sponsor: Brown University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2018-10-23
• Study First Submitted QC: 2018-10-23
• Study First Posted: 2018-10-25
• Study Start: 2019-07-01
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-10
• Last Update Posted: 2020-04-13
• Primary Completion: 2022-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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:

  1. high central nervous system International Prognostic Index,
  2. testicular, breast, or uterine involvement,
  3. dual expresser or double/triple-hit status,
  4. HIV positive status, or
  5. Molecularly defined high-risk subtype.

Exclusion Criteria

• pregancy
• unable to provide informed consent
• significant comorbidity in the investigator's judgement

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CNS prophylaxis protocol	Methotrexate	Patients will receive central nervous system prophylaxis protocol using high-dose methotrexate and cytarabine.
CNS prophylaxis protocol	Cytarabine	Patients will receive central nervous system prophylaxis protocol using high-dose methotrexate and cytarabine.

Primary Outcome Measures

Name	Time	Method
Proportion with clinically significant toxicity	1 year	Clinically significant toxicity as defined in the protocol

Secondary Outcome Measures

Name	Time	Method
Cumulative incidence of central nervous system recurrence	2 years	Cumulative incidence of central nervous system recurrence

Trial Locations

Locations (1)

Roxanne Wood; 🇺🇸 Providence, Rhode Island, United States