Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen
|Leukemia Hodgkin Lymphoma Non-Hodgkin Lymphoma Multiple Myeloma Myelodysplastic Syndrome||Drug: Clofarabine/Busulfan x 4 Procedure: Peripheral blood stem cell transplant Radiation: Total Lymphoid Irradiation||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen|
- Regimen Related Toxicities [ Time Frame: two years ]The incidence of non-hematological toxicities (Common Terminology Criteria for Adverse Events (CTCAE) 3.0) from initiation of conditioning to Day + 30 or toxicities after day +30, possibly, probably or definitely related to conditioning for all patients treated with Clofarabine (independent of dose level).
- One-year Overall Survival Rate for AML [ Time Frame: 1 year ]Percent Overall Survival (OS) for at one year for subjects with Acute Myeloid Leukemia (AML).
- Two-year Overall Survival for All Cases. [ Time Frame: 2 years ]Percent Overall Survival (OS) at two years for all patients.
- Five-year Overall and Disease-free Survival of All Cases. [ Time Frame: five years ]
|Study Start Date:||October 2007|
|Study Completion Date:||September 2012|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Study will start at the 2nd dose level of three Clofarabine levels, in combination with Busulfan. The Clofarabine level that each subsequent patient is treated at is determined by a method using continual reassessment.
After pre-conditioning, subjects will receive a peripheral blood stem cell transplant.
Drug: Clofarabine/Busulfan x 4
Procedure: Peripheral blood stem cell transplant
Clofarabine IV (dose levels)
Busulfan IV 3.2 mg/kg daily x 4 days
Peripheral blood stem cell transplant, after pre-conditioning drug treatmentRadiation: Total Lymphoid Irradiation
Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant
Transplants with stem cells collected from the blood of an unrelated donor (allo-HSCT) are being used more commonly for many blood cancers which are not curable with more conventional methods of chemotherapy. Although allo-HSCT has great potential, there are still high risks due to infections, graft-versus-host disease (GVHD), where the donor's cells attack the recipient's tissues as foreign, and due to toxic effects of the chemotherapy drugs given to prepare (or condition) the recipient's bone marrow for transplant.
As a reduced intensity conditioning, a combination of Fludarabine and a lower dose of Busulfan (Flu/BU2) is one of the most popular regimens. Among full-intensity regimens, a combination of Fludarabine and standard-dose Busulfan (Flu/BU4) has been investigated recently and shown to be very well tolerated.
Clofarabine, similar to Fludarabine, is known to have a stronger anti-tumor effect than Fludarabine and has shown promise in treating aggressive acute leukemias. In addition, evidence is that it is well-tolerated with manageable side effects especially in older subjects. Thus replacing Fludarabine with Clofarabine in a full-intensity transplant regimen, Clo/BU4 may provide a regimen with increased anti-tumor activity without adding significant risks of toxicity.
The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity regimen (Clo/BU4) and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for HSCT in the treatment for aggressive hematologic malignancies, in subjects where more conventional approaches are failing.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00556452
|United States, Michigan|
|University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program|
|Ann Arbor, Michigan, United States, 48170|
|Principal Investigator:||John Magenau, M.D.||University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program|