Clinical trial NCT00556452
Conditions: Leukemia Hodgkin Lymphoma Non-Hodgkin Lymphoma Multiple Myeloma Myelodysplastic Syndrome
Sponsor: University of Michigan Rogel Cancer Center
Start date: 2007-10-01; Completion date: 2012-09-01
Enrollment: 46 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with Busulfan as a full-intensity conditioning (Clo/BU4 regimen) prior to transplant and then (Phase II) to investigate the safety and effectiveness of this regimen as a conditioning for stem cell transplant in the treatment of aggressive hematologic malignancies in subjects where more conventional approaches are failing.

Detailed description:
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.

Arms: arm 1: 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.
Interventions: intervention 1: Clofarabine/Busulfan x 4 intervention 2: Peripheral blood stem cell transplant intervention 3: Total Lymphoid Irradiation
Intervention descriptions: intervention 1: Clofarabine IV (dose levels)

* 1st dose level: 20 mg/m2/day x 5 days
* 2nd dose level: 30 mg/m2/day x 5 days
* 3rd dose level: 40 mg/m2/day x 5 days

Busulfan IV 3.2 mg/kg daily x 4 days intervention 2: Peripheral blood stem cell transplant, after pre-conditioning drug treatment intervention 3: Total Lymphoid Irradiation (TLI) of 4 Gy, if cord blood transplant

Protocol documents: