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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00660400
• Other study ID #: MCC-15158
• Secondary ID: 106349
• Status: Completed
• Phase: N/A
• First received: April 16, 2008
• Last updated: September 11, 2014
• Start date: March 2008
• Est. completion date: June 2014

Study information

• Verified date: September 2014
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 68 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• 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.

Procedure:
• 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.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Relapse-free Survival (RFS)	Relapse-free survival one year after allogeneic HCT in MDS patients receiving at least one complete cycle of 5-azacitidine (Vidaza) in the pre-transplantation setting. Relapsed disease: if with complete remission (CR) - greater than 5% blasts in bone marrow; if with partial response (PR) - greater than 30% increase in blasts in the marrow; if with stable disease (SD) - return to pretreatment peripheral blood levels and transfusion requirements due to disease.	One year post allogeneic HCT	Yes
Secondary	Overall Response Rate (ORR)	Pre-allogeneic HCT responses to 5-azacitidine (Vidaza), based on the International Working Group criteria: Complete Remission (CR); Partial Response (PR); Stable Disease (SD). Point estimates and 95% confidence intervals were calculated for the response rate to 5-azacitidine, evaluated at marrow evaluation after 4 cycles of 5-azacitidine or prior to HCT whichever came first. CR: Bone marrow with 5% myeloblasts and normal maturation of all cell lines. PR: All CR criteria if abnormal before treatment except bone marrow blasts decreased by 50% over pretreatment but still > 5%. SD: Failure to attain CR, PR, relapsed (or progressive) disease.	At the end of up to six (28 day) cycles of 5-azacitidine	No
Secondary	Percentage of Participants Who Proceed to Hematopoietic Cell Transplantation (HCT)	Proportion of patients enrolled who subsequently proceeded to allogeneic HCT.	Up to 3 years	No
Secondary	Percentage of Participants With Overall Survival (OS)	Overall survival for all participants at one year after first dose of 5-azacitidine (Vidaza). Overall survival was calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.	One year	No

External Links

•   Moffitt Cancer Center Clinical Trials website