Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome Who Are Candidates For Allogeneic Hematopoietic Cell Transplant

NCT ID: NCT00660400

Last Updated: 2014-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2014-06-30

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.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combined Therapy

5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).

Group Type: EXPERIMENTAL

5-azacitidine

Intervention Type: DRUG

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.

Allogeneic Hematopoietic Cell Transplantation (HCT)

Intervention Type: PROCEDURE

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.

Interventions

5-azacitidine

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 Type: DRUG

Allogeneic Hematopoietic Cell Transplantation (HCT)

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.

Intervention Type: PROCEDURE

Other Intervention Names

Vidaza; HCT

Eligibility 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 glutamic pyruvic 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teresa Field, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Janelle Perkins, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Countries

United States

References

Nishihori T, Perkins J, Mishra A, Komrokji R, Kim J, Kharfan-Dabaja MA, Perez L, Lancet J, Fernandez H, List A, Anasetti C, Field T. Pretransplantation 5-azacitidine in high-risk myelodysplastic syndrome. Biol Blood Marrow Transplant. 2014 Jun;20(6):776-80. doi: 10.1016/j.bbmt.2014.02.008. Epub 2014 Feb 15.

Reference Type: DERIVED

PMID: 24534108 (View on PubMed)

Other Identifiers

106349

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-15158

Identifier Type: -

Identifier Source: org_study_id