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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

Primary Purpose

Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
low dose 5'-azacitidine
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes (MDS) focused on measuring 5'-Azacitidine, Stem cell transplant, 13-192

Eligibility Criteria

1 Year - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering at Basking Ridge (Consent and Follow-up)
  • Memorial Sloan Kettering Monmouth (Consent and Follow-up)
  • Memorial Sloan Kettering Bergen (Consent and Follow-up)
  • Memorial Sloan Kettering Commack (Consent and Follow-up)
  • Memorial Sloan Kettering Westchester (Consent and Follow-up)
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau (Consent and Follow-up)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

low dose 5'-azacitidine

Arm Description

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.

Outcomes

Primary Outcome Measures

relapse rate
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
Kaplan-Meier methodology will be used to compare overall survival.
safety
The safety will be described by tabulating the number of transfusions, frequencies of bleeding and serious infections, and the use of G-CSF support.

Full Information

First Posted
November 21, 2013
Last Updated
September 28, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01995578
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
September 27, 2023 (Actual)
Study Completion Date
September 27, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML)
Keywords
5'-Azacitidine, Stem cell transplant, 13-192

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
low dose 5'-azacitidine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
low dose 5'-azacitidine
Intervention Description
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. Patients who come off-study for reasons unrelated to toxicities before completing 4 cycles will be replaced 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.
Primary Outcome Measure Information:
Title
relapse rate
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
overall survival
Description
Kaplan-Meier methodology will be used to compare overall survival.
Time Frame
2 years
Title
safety
Description
The safety will be described by tabulating the number of transfusions, frequencies of bleeding and serious infections, and the use of G-CSF support.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roni Tamari, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering at Basking Ridge (Consent and Follow-up)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth (Consent and Follow-up)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen (Consent and Follow-up)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack (Consent and Follow-up)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester (Consent and Follow-up)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau (Consent and Follow-up)
City
Rockville Centre
State/Province
New York
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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