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

NCT01995578 | Completed Phase 2 Results

• 1 other identifier: 13-192
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

5'-Azacitidine; Stem cell transplant; 13-192

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Overall Survival

  2 years

• Number of Participants Evaluated for Treatment Safety

  2 years

Study Arms (1)

low dose 5'-azacitidine

EXPERIMENTAL

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

Interventions

low dose 5'-azacitidine DRUG

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.

low dose 5'-azacitidine

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Consent and Follow-up)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Consent and Follow-up)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Consent and Follow-up)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (Consent and Follow-up)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Consent and Follow-up)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Consent and Follow-up)

Rockville Centre, New York, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Dr. Roni Tamari MD
• Organization: Memorial Sloan Kettering Cancer Center

tamarir@mskcc.org

646-608-3738

Study Officials

• Roni Tamari, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2013
• First Posted: November 26, 2013
• Study Start: December 1, 2013
• Primary Completion: September 27, 2023
• Study Completion: September 27, 2023
• Last Updated: May 22, 2024
• Results First Posted: May 22, 2024

Record last verified: 2023-09

Locations

US (7)