The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory CNS Lymphoma (DRBEAT)
The primary purpose of the study will be testing the dosing of temozolomide to find the target dose that a person can tolerate. The other part of the study will be determining how helpful it can be to CNS lymphoma patients by adding temozolomide to the "conditioning regimen" prior to stem cell transplantation.
This research study is designed to test the investigational use of temozolomide as part of a conditioning regimen prior to stem cell transplantation. This drug has not yet been approved by the U.S. Food and Drug Administration (FDA) to be used in the setting of stem cell transplantation in lymphomas of the brain (central nervous system or CNS) but it has been studied and used before in transplantation with reasonable results.
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 2a Study of the Addition of Temozolomide to a Standard Conditioning Regimen for Autologous Stem Cell Transplantation in Relapsed and Refractory Central Nervous System (CNS) Lymphoma|
- Efficacy of the DRBEAT Regimen [ Time Frame: One Year ]
Efficacy of the DRBEAT Regimen will be assessed by analysis of
one-year progression-free survival (PFS), defined as the time interval from maximal response from therapy to tumor regrowth, progression, or death,
- Overall survival, defined as the time interval between the date of transplant and the date of death from any cause.
- Safest dose of temozolomide for the DRBEAT Regimen [ Time Frame: One year ]Safety will be assessed using a dose escalation design for temozolomide's use to determine the target dose and also to evaluate any and all acute treatment related toxicities. During the course of patient follow up and therapy, toxicities will be evaluated, particularly as the investigators will be determining the target dose of temozolomide. One of the major criteria for dose limiting toxicity for the study will be any Grade 3 or 4 nonhematologic toxicity from a list of commonly expected toxicities associated with autologous transplantation and temozolomide.
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
|Experimental: DRBEAT Regimen||
The DRBEAT regimen will be similar to RBEAM. Rituximab and Carmustine will be given Day -6. Etoposide and Cytarabine will be given on Days -5 to -2. Temozolomide will be given via divided doses over five days starting on Day -5 to Day -1. A dose escalation design, known as EWOC (Escalation with overdose control) will be used to determine the target dose of temozolomide for this study. The starting dose given over five days will begin at 250mg/m2 (cumulative total dose of 1250 mg/m2), as previous data indicates this to be a safe dose. Based on the reported Dose Limiting toxicities from the previous patients, the EWOC statistical modeling will be performed to determine the next dose level.
Currently there is no standard of care for relapsed or refractory primary central nervous system (CNS) lymphoma. After high-dose methotrexate or radiation therapy, the best approach to relapsed disease is undefined. Common practice is the regimen RBEAM as a conditioning regimen in this patient population prior to transplantation. The RBEAM regimen includes R (rituximab), B (BCNU), E (etoposide), A (Ara-C (cytarabine)) and M (melphalan). In addition, dexamethasone is included in the regimen although not noted in the RBEAM mnemonic. However, the melphalan used in this combination is not thought to have much CNS penetration. Therefore, temozolomide, an alkylating agent known to penetrate the CNS and approved by the FDA for brain tumors will be used and evaluated in this study instead of melphalan.
The aim of this study is to determine an effective and safe dose of temozolomide orally administered to patients with relapsed primary CNS lymphoma over the 5 days preceding autologous stem-cell transplantation. The hope is that the conditioning regimen DRBEAT [D (dexamethasone) (R (rituximab), B (BCNU), E (etoposide), A (Ara-C (cytarabine)) and T (temozolomide)] will significantly improve the survival of patients with relapsed CNS lymphoma.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01235793
|Contact: Sarah Zacharia||310-423-0277||Sarah.Zacharia@cshs.org|
|United States, California|
|Cedars Sinai Medical Center||Recruiting|
|Los Angeles, California, United States, 90048|
|Contact: Sarah Zacharia 310-423-0277 Sarah.Zacharia@cshs.orgs.org|
|Sub-Investigator: Jethro Hu, MD|
|Sub-Investigator: Yuliya Linhares, MD|
|Sub-Investigator: Jeremy Rudnick, MD|
|Principal Investigator: Michael Lill, MD|
|Sub-Investigator: Noah Merin, MD|
|Principal Investigator:||Michael Lill, MD||Cedars-Sinai Medical Center|
|Principal Investigator:||Yuliya Linhares, MD||Cedars-Sinai Medical Center|