Maintenance Low Dose 5'-Azacitidine Post T Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Myelodysplastic Syndrome and Acute Myelogenous Leukemia With High Risk for Post-Transplant Relapse

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01995578
First received: November 21, 2013
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to learn if 5'-Azacitidine will help to lower the risk of the disease coming back after a stem cell transplant in patients with MDS and AML. This study will also be looking at the side effects of this medicine.

5'-Azacitidine is an FDA approved drug for treatment of MDS and AML, as well as patients whose disease came back after transplant, where it helped going into remission. It is unclear if 5'-Azacitidine can prevent the disease from coming back after transplant. This study will help show if getting 5'-Azacitidine soon after transplant can lower the risk of your disease coming back.


Condition Intervention Phase
Myelodysplastic Syndromes (MDS)
Acute Myelogenous Leukemia (AML)
Drug: low dose 5'-azacitidine
Phase 2

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 Single Arm Phase II Trial of Maintenance Low Dose 5'-Azacitidine Post T Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Myelodysplastic Syndrome and Acute Myelogenous Leukemia With High Risk for Post-Transplant Relapse

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • relapse rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Relapse of MDS or AML will be analyzed as to type and genetic origin of the leukemic cells. These will be defined by morphologic and/or cytogenetic criteria: an increasing number of blasts in the marrow over 5%, by presence of circulating blasts, or by presence of blasts in any extramedullary site as well as presence of previous cytogenetic abnormalities. Other studies assessing for MRD, FACS and FISH assays will be evaluated but would not be considered disease relapse if positive since they are experimental.


Secondary Outcome Measures:
  • overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier methodology will be used to compare overall survival.

  • safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    The safety will be described by tabulating the number of transfusions, frequencies of bleeding and serious infections, and the use of G-CSF support.


Estimated Enrollment: 32
Study Start Date: December 2013
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: low dose 5'-azacitidine
This is a single arm phase II trial to assess the efficacy and confirm the safety of maintenance therapy with 5'-azacitadine compared to historical control after TCD allogeneic hematopoietic stem cell transplant for patients with MDS and AML who are at high risk of relapse.
Drug: low dose 5'-azacitidine
5'-azacitadine will be given at a low dose of 32mg/m2 S.C for 5 days every 28 days (a cycle). Dose de-escalation will be permitted for hematologic and non- hematologic toxicities. Patients will start taking the study drug between days 60-120 post TCD allogeneic hematopoietic stem cell transplant and up to a year post-transplant or until there is a toxicity that requires cessation of therapy. Therefore patients will get between 8-10 cycles. Since most cases of relapse occur early post transplant, in the first year, this is the most appropriate time to intervene. Treatment will start as soon as possible.

  Eligibility

Ages Eligible for Study:   1 Year to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients who have undergone T cell depleted allogeneic hematopoietic stem cell transplantation at MSKCC for:

  • De novo myelodysplastic syndromes (MDS): IPSS-1 with poor risk cytogenetics or higher IPSS.
  • Acute myelogenous leukemia (AML) in first remission that required more than 1 cycle of treatment to achieve remission or with the following cytogenetic abnormalities: FLT3 mutation, deletion/monosomy of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities. Also patients in second or greater remission.
  • Patients with Secondary MDS/AML.
  • Patients will be considered eligible for the study if after transplant they achieved hematologic (<5% blasts) and cytogenetic remission.
  • Patients will be eligible to enter the study between 60-120 days post transplant.
  • Age: pediatrics and adults patients - 1 year old-75 years old.
  • Karnofsky performance status >=60% for patients >16yo and Lansky performance status >=60% for patients ≤16yo
  • Stable blood counts (ANC>1000/uL, Hb>8gr/dL, Plt>50,000/ uL) not supported by transfusions.
  • Renal: Serum creatinine <1.5 ULN
  • Hepatic: <3xULN ALT and <1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
  • Cardiac: Adequate cardiac function measured by LVEF>50%. If asymptomatic, pretransplant echocardiogram is adequate. If symptomatic, echocardiogram needs to be repeated.
  • Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

Patients will be excluded from the trial if at time of enrollment:

  • Active uncontrolled bacterial, fungal or viral infection.
  • Evidence of uncontrolled graft-versus-host disease.
  • Pulmonary: new onset hypoxia
  • Known or suspected hypersensitivity to 5'-azacitadine or mannitol.

    • Evidence of residual disease either by increased blasts count (>5%) or persistence of previous known cytogenetics abnormalities.
  • Peripheral blood neutrophil chimerism: less than 95% donor.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01995578

Contacts
Contact: Roni Tamari, MD 212-639-5987
Contact: Hugo Castro-Malaspina, MD 212-639-8197

Locations
United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Roni Tamari, MD    212-639-5987      
Contact: , MD         
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Roni Tamari, MD    212-639-5987      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Roni Tamari, MD    212-639-5987      
Contact: Hugo Castro-Malaspina, MD    212-639-8197      
Principal Investigator: Roni Tamari, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Roni Tamari, MD    212-639-5987      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Roni Tamari, MD    212-639-5987      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Roni Tamari, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01995578     History of Changes
Other Study ID Numbers: 13-192
Study First Received: November 21, 2013
Last Updated: May 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
5'-Azacitidine
Stem cell transplant
13-192

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
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 July 20, 2014