Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome (MDS) Who Are Candidates For Allogeneic Hematopoietic Cell Transplant - Full Text View

Sponsor:	H. Lee Moffitt Cancer Center and Research Institute
Collaborator:	Celgene Corporation
Information provided by (Responsible Party):	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00660400

Purpose

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.

Condition	Intervention
Leukemia	Drug: 5-azacitidine Procedure: Allogeneic Hematopoietic cell transplantation

Study Type:	Interventional
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 Who Are Candidates For Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Azacitidine

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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.
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,, time to progression of MDS, time to progression to AML 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 ]
Overall survival,, time to progression of MDS, time to progression to AML 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 ]
Overall survival,, time to progression of MDS, time to progression to AML will be calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.

Enrollment:	25
Study Start Date:	March 2008
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Chemotherapy	Drug: 5-azacitidine Once enrolled, the patients will receive pre-transplant Vidaza (5-azacitidine) 75 mg/M2/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 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 Vidaza 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 Vidaza 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 posttransplant. Other Name: HCT

Arms

Assigned Interventions

Experimental: Chemotherapy

Drug: 5-azacitidine

Once enrolled, the patients will receive pre-transplant Vidaza (5-azacitidine) 75 mg/M2/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

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 Vidaza 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 Vidaza 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 posttransplant.

Other Name: HCT

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 Vidaza will be given per standard practice.
Vidaza dose is 75 mg/M2/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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 68 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Potential candidate for HCT.
Histologically confirmed diagnosis by pathologic review of previous diagnosis of high-risk myelodysplastic syndrome (MDS): International Prognostic Scoring System (IPSS) > 1 or AML-MDS or treatment related MDS.
Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis; Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamicpyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels ≤2 x ULN.
Serum creatinine levels ≤1.5 x ULN
Karnofsky performance status greater or equal to 70%
Signed informed consent form in accordance with institutional policies

Exclusion Criteria:

Known or suspected hypersensitivity to Vidaza or mannitol
Pregnant or lactating women
Human immunodeficiency virus (HIV) or seropositive, confirmed by nucleic acid amplification testing (NAT)
Active central nervous system (CNS) malignancy
Active infection
History or presence of primary hepatoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660400

Locations

United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Celgene Corporation

Investigators

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

More Information

Additional Information:

Moffitt Cancer Center Trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00660400 History of Changes
Other Study ID Numbers:	MCC-15158, 106349
Study First Received:	April 16, 2008
Last Updated:	October 10, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Myeloid
Monocytic

Additional relevant MeSH terms:

Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012