Early Systemic Central Nervous System Prophylaxis in Diffuse Large B-cell Lymphoma (BrUOG-377)

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

Study Overview

• Status: Withdrawn
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Methotrexate; Drug: Cytarabine

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Roxanne Wood

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CNS prophylaxis protocol; Patients will receive central nervous system prophylaxis protocol using high-dose methotrexate and cytarabine.	Drug: Methotrexate; Systemic methotrexate; Other Names: Methotrexate sodium; Drug: Cytarabine; Systemic cytarabine; Other Names: Cytosar-U

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brown University

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (Actual): October 25, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2020
• Last Update Submitted That Met QC Criteria: April 10, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cytarabine; Methotrexate
• Other Study ID Numbers: BrUOG-377

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No