Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome Who Are Candidates For Allogeneic Hematopoietic Cell Transplant
The purpose of this study is to find out if treating people who have high-risk myelodysplastic syndrome (MDS) with Vidaza (also called 5-azacitidine) prior to their allogeneic hematopoietic cell transplant (HCT) is helpful in preventing their myelodysplastic syndrome from coming back.
In previous research, Vidaza 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. Vidaza is approved by the Food and Drug Administration (FDA) for the treatment of MDS. The effect of Vidaza in patients receiving hematopoietic cell transplants have not been studied.
Procedure: Allogeneic Hematopoietic Cell Transplantation (HCT)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study Of Pre-Transplant 5-Azacitidine (Vidaza) In Patients With High-Risk Myelodysplastic Syndrome (MDS) Who Are Candidates For Allogeneic Hematopoietic Cell Transplantation|
- Number of Participants With Progression Free Survival (PFS) [ Time Frame: One year ] [ Designated as safety issue: Yes ]Evaluate progression free survival at one year after allogeneic hematopoietic cell transplantation (HCT) in patients receiving at least one complete cycle of Vidaza in the pretransplant setting. Progression-free survival time will be calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.
- Number of Participants With Desired Response [ Time Frame: 18 months ] [ Designated as safety issue: No ]Response rate to Vidaza. Point estimates and 95% confidence intervals will be calculated for the response rate to Vidaza, evaluated at marrow evaluation after 4 cycles of Vidaza or prior to HCT whichever comes first. Complete remission (CR): Bone marrow with 5% myeloblasts and normal maturation of all cell lines. Partial response (PR): All CR criteria if abnormal before treatment except bone marrow blasts decreased by 50% over pretreatment but still > 5%. Improved: Mono- or bilineage response in peripheral blood counts and transfusion requirements less than 50% of baseline.
- Number of Participants Who Proceed to HCT [ Time Frame: 18 months ] [ Designated as safety issue: No ]Proportion of patients enrolled who subsequently proceed to HCT. Point estimates and 95% confidence intervals will also be calculated for the proportion of patients treated with Vidaza who are transplanted. Descriptions of reasons for not coming to transplant will be tabulated.
- Number of Participants With Overall Survival (OS) [ Time Frame: One year ] [ Designated as safety issue: No ]Overall survival for all participants at one year after first dose of Vidaza. Overall survival will be calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.
- Time to Progression of MDS [ Time Frame: 18 months ] [ Designated as safety issue: No ]Time to progression of MDS will be calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.
- Time to Progression to AML [ Time Frame: 18 months ] [ Designated as safety issue: No ]Time to progression to AML will be calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.
|Study Start Date:||March 2008|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Once enrolled, the patients will receive pre-transplant Vidaza (5-azacitidine) 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.
Other Name: Vidaza
|Experimental: Bone Marrow Transplant||
Procedure: Allogeneic Hematopoietic Cell Transplantation (HCT)
Patients will receive transplantation if there is either a suitable sibling or an unrelated donor.
Other Name: HCT
- 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 Vidaza will be given per standard practice.
- Vidaza 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 Vidaza 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 Vidaza 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 Vidaza.
- As the number of cycles of Vidaza is not standardized and the retrospective review of our patients noted above indicated a benefit to ANY exposure to Vidaza, the actual number of cycles of Vidaza 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 Vidaza before transplant, or after the fourth cycle of Vidaza, 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.
- 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.
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Teresa Field, M.D., Ph.D.||H. Lee Moffitt Cancer Center and Research Institute|
|Principal Investigator:||Janelle Perkins, Pharm.D.||H. Lee Moffitt Cancer Center and Research Institute|