Clinical trial NCT00660400: Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome Who Are Candidates For Allogeneic Hematopoietic Cell Transplant
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Leukemia
Keywords: Myeloid
Monocytic
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2008-04-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Relapse-free Survival (RFS)
timeFrame: One year post allogeneic HCT
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: At the end of up to six (28 day) cycles of 5-azacitidine
measure: Percentage of Participants Who Proceed to Hematopoietic Cell Transplantation (HCT)
timeFrame: Up to 3 years
measure: Percentage of Participants With Overall Survival (OS)
timeFrame: One year
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Teresa Field, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Janelle Perkins, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.