Last updated on October 2018

IMRT-TMI With Fludarabine as Myeloablative Conditioning for Allogeneic HSCT

Brief description of study

The purpose of this study is to find the maximum tolerated dose (MTD) of Total Marrow Irradiation (TMI), a type of radiation treatment administered with fludarabine, a type of chemotherapy to prepare patients for allogeneic hematopoietic stem cell transplantation (Allo-HSCT). The study will also examine the efficacy of fludarabine and total marrow radiation treatment. Patients in this study will receive fludarabine and TMI during their conditioning regimen for 7 days prior to Allo-HSCT

Detailed Study Description

This is a phase I/II clinical trial to determine the maximum tolerated dose (MTD) of intensity modulated radiation therapy based total marrow irradiation (TMI) in combination with fludarabine in the context of a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (Allo-HSCT), as well as to determine the efficacy of the regimen in patients with high-risk and relapsed or refractory leukemia and myelodysplasia. TMI, which allows for conformal dosing of target bone marrow tissue while giving lower doses to organs at risk, is considered by many to be a superior alternative to conventional total body irradiation (TBI)

Primary Objectives:

Phase I component:

Determine the MTD of TMI given concurrently with fludarabine (fixed at 150 mg/m2) as a conditioning regimen for Allo-HSCT for patients with high risk (relapsed/refractory) acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelogenous leukemia (CML).

Phase II component:

Single-arm exploratory study to expand the cohort at the MTD level to estimate 1- year overall survival (OS), with the objective of increasing the OS from the historical rate of 30% (null hypothesis ) to 50% (alternate hypothesis) with 80% power and a one-sided type I error of 0.05.

Secondary Objectives

  1. Describe the extramedullary toxicity and the incidence of complications, including mucositis, acute and chronic graft versus host disease (GvHD), sinusoidal obstruction syndrome (SOS), and pneumonitis.
  2. Describe the time to engraftment of neutrophils and platelets
  3. Describe the disease response rate at day 30 after transplantation
  4. Describe the overall survival and disease-free survival
  5. Describe the cumulative incidence of relapse and non-relapse mortality
  6. Determine the correlation between plasma/serum markers and radiation induced acute and long term toxicities.

Clinical Study Identifier: NCT03696537

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Recruitment Status: Open

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