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

Sponsors and Collaborators:	H. Lee Moffitt Cancer Center and Research Institute Celgene Corporation
Information provided by:	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 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 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:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
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, Adult Acute Leukemia, Adult Chronic

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:

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. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Assessing the response to Vidaza, proportion of patients enrolled who subsequently proceed to HCT, overall survival and disease-free survival at 1 year, time to progression of MDS, and time to progression to AML. [ Time Frame: Dependent upon results ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
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
1: Experimental	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.
2: Experimental	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.

Arms

Assigned Interventions

1: Experimental

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.

2: Experimental

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.

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 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 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
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 range for the laboratory (ULN). 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
HIV or seropositive, confirmed by NAT
Active CNS malignancy
Active infection
History or presence of primary hepatoma

Contacts and Locations

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

Contacts

Contact: Teresa Field, M.D., Ph.D.	813-745-7202	teresa.field@moffitt.org
Contact: Robin Lavaron	813-745-6040	robin.lavaron@moffitt.org

Locations

United States, Florida
H. Lee Moffitt Cancer Center & Research Institute	Recruiting
Tampa, Florida, United States, 33612
Contact: Teresa Field, M.D., Ph.D. 813-745-7202 teresa.field@moffitt.org
Contact: Robin Lavaron 813-745-6040 robin.lavaron@moffitt.org
Principal Investigator: Teresa Field, M.D., Ph.D.
Principal Investigator: Janelle Perkins, Pharm.D.
Sub-Investigator: Claudio Anasetti, M.D.
Sub-Investigator: Ernesto Ayala, M.D.
Sub-Investigator: Hugo Fernandez, M.D.
Sub-Investigator: Mohamed Kharfan-Dabaja, M.D.
Sub-Investigator: Jeffrey Lancet, M.D.
Sub-Investigator: Alan List, M.D.
Sub-Investigator: Jose Ochoa-Bayona, M.D.
Sub-Investigator: Lia Perez, M.D.
Sub-Investigator: Jyoti Raychaudhuri, M.D.
Sub-Investigator: Daniel Sullivan, M.D.

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 & Research Institute, Inc. ( Teresa Field, M.D., Ph.D. )
Study ID Numbers:	MCC-15158, USF IRB-106349
Study First Received:	April 16, 2008
Last Updated:	January 30, 2009
ClinicalTrials.gov Identifier:	NCT00660400 History of Changes
Health Authority:	United States: Institutional Review Board

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

Myeloid
Monocytic

Study placed in the following topic categories:

Antimetabolites
Leukemia
Preleukemia
Precancerous Conditions

Hematologic Diseases
Myelodysplastic Syndromes
Azacitidine
Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Precancerous Conditions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hematologic Diseases
Myelodysplastic Syndromes

Enzyme Inhibitors
Pharmacologic Actions
Leukemia
Preleukemia
Neoplasms
Therapeutic Uses
Azacitidine
Bone Marrow Diseases

ClinicalTrials.gov processed this record on July 02, 2009