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

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

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes (MDS); Acute Myelogenous Leukemia (AML)
• Intervention / Treatment: Drug: low dose 5'-azacitidine

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering at Basking Ridge (Consent and Follow-up)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Consent and Follow-Up)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Consent and Follow-Up)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack (Consent and Follow-Up)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Consent and Follow-Up)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States
      • Memorial Sloan Kettering Nassau (Consent and Follow-up)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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. 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	Kaplan-Meier methodology will be used to compare overall survival.	2 years
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.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Roni Tamari, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): September 27, 2023
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: November 21, 2013
• First Posted (Estimated): November 26, 2013

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Stem cell transplant; 5'-Azacitidine; 13-192
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: 13-192