Clinical trial NCT00660400
Conditions: Leukemia
Keywords: Myeloid Monocytic
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2008-03-01; Completion date: 2014-06-01
Enrollment: 25 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with 5-Azacitidine (Vidaza) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back.

In previous research, 5-Azacitidine appeared to help the bone marrow of a patient with MDS begin to function more normally. This means bone marrow cells can grow and do their work the way they were meant to. 5-Azacitidine is approved by the Food and Drug Administration (FDA) for the treatment of MDS. The effect of 5-Azacitidine in patients receiving hematopoietic cell transplants have not been studied.

Detailed description:
RESEARCH PLAN

* This will be a single-center prospective trial
* Patients with high risk MDS that are potentially eligible for HCT will be enrolled.
* A donor search will be initiated, and 5-Azacitidine will be given per standard practice.
* 5-Azacitidine dose is 75 mg/M\^2/day subcutaneously by standard practice (generally this is 7 days per monthly cycle, but alterations occur depending on clinical and laboratory parameters).
* Patients where a suitable donor is not found can continue with 5-Azacitidine per standard treatment. These patients will be followed until progression of MDS to acute myelogenous leukemia (AML) or death, for up to one year.
* If a suitable donor is obtained, the patient will proceed to HCT. The HCT conditioning regimen will be dictated by the Blood and Marrow Transplant (BMT) physician. While waiting HCT, additional cycles 5-Azacitidine may be given. Pre-HCT conditioning regimen therapy will begin no more than 8 weeks and no less than 4 weeks after the last administration of 5-Azacitidine.
* As the number of cycles of 5-Azacitidine is not standardized and the retrospective review of our patients noted above indicated a benefit to ANY exposure to 5-Azacitidine, the actual number of cycles of 5-Azacitidine delivered will not be specified. In addition, as high risk MDS patients have an average time to death of 0.4 years, any delay to HCT once it is available is to be avoided.
* A bone marrow biopsy will be performed to reassess disease response to therapy after the last cycle of 5-Azacitidine before transplant, or after the fourth cycle of 5-Azacitidine, whichever comes first. Note that both the biopsy and the timing of the biopsy is a standard evaluation procedure.
* Donor progenitor cell collection will be prescribed by the BMT Attending Physician.

HCT

* The patient will undergo HCT designated per attending BMT physician.
* Supportive care will be based on institutional guidelines, Stem cell collections, processing and laboratory studies

Stem cell collections, processing and laboratory studies

* Graft assessment, processing, and characterization will be done as per institutional guidelines
* Chimerism testing will be obtained to document post-transplant engraftment, per standard practice.

Arms: arm 1: 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Interventions: intervention 1: 5-azacitidine intervention 2: Allogeneic Hematopoietic Cell Transplantation (HCT)
Intervention descriptions: intervention 1: Once enrolled, the patients will receive pre-transplant 5-azacitidine (Vidaza) 75 mg/M\^2/day subcutaneously for 5-7 days every 28 days). Adjustments in dose and timing may occur based on clinical and hematological parameters. intervention 2: Patients will receive transplantation if there is either a suitable sibling or an unrelated donor.

* Response will be evaluated by bone marrow biopsy after 4 cycles of 5-azacitidine or prior to HCT whichever comes first. Due to the very high risk of progression to AML or death in this patient population, the HCT will be done as soon as possible.
* The patients may have additional cycles of 5-azacitidine per standard hematology practice until scheduled for transplant or until progression of disease.
* All patients will be followed until time to progression of MDS, AML or death or a maximum of 1 year. For patients that are transplanted, follow up will be to one year post-transplant.

Protocol documents: