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A Phase II Study of 5-Azacitidine and Sargramostim as Maintenance Treatment After Definitive Therapy for Poor-risk AML or MDS

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01700673
First received: October 2, 2012
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

We propose a phase II study to determine the impact of maintenance therapy with 5-azacytidine and GM-CSF in patients with poor-risk AML or MDS, who are in remission after definitive treatment with either stem cell transplant or cytarabine-based consolidation chemotherapy.

In order to precede relapse and to avoid lead time bias, treatment would need to commence within 185 days of definitive therapy. Furthermore, approximately 50% of relapses occur within the first year and up to 80% within two years after SCT, therefore we would limit the duration of maintenance therapy to one year, followed by two years of follow-up.


Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: 5-azacitidine and sargramostim
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of 5-Azacitidine (5AC) in Combination With Sargramostim (GM-CSF) as Maintenance Treatment, After Definitive Therapy With Either Stem Cell Transplant (SCT) or Cytarabine-based Chemotherapy, in Patients With Poor-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • To evaluate the 2 year relapse free survival of patients [ Time Frame: 2 year ] [ Designated as safety issue: No ]
    to evaluate the two-year relapse-free survival (RFS) of patients with poor-risk Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS), who receive maintenance treatment with 5-Azacytidine(5AC) in combination with GM-CSF during remission, following definitive therapy with either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy.


Secondary Outcome Measures:
  • 1. Describe and quantify the toxicity profile of the combination of 5AC and GM-CSF [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    1. Describe and quantify the toxicity profile of the combination of 5AC and GM-CSF

  • 2. Determine the impact on one-year RFS and overall survival for poor-risk myeloid disorders following maintenance therapy with 5AC and GM-CSF [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    2. Determine the impact on one-year RFS and overall survival for poor-risk myeloid disorders following maintenance therapy with 5AC and GM-CSF


Estimated Enrollment: 75
Study Start Date: June 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARM 1
5-azacitidine and sargramostim after myeloablative stem cell transplant
Drug: 5-azacitidine and sargramostim
5-azacitidine will be administered days 1-5 of a 28 day cycle. sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Other Name: Vidaza, GM-CSF
Experimental: Arm 2
5-azacitidine and sargramostim after non-myeloablative stem cell transplant
Drug: 5-azacitidine and sargramostim
5-azacitidine will be administered days 1-5 of a 28 day cycle. sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Other Name: Vidaza, GM-CSF
Experimental: Arm 3
5-azacitidine and sargramostim after standard consolidation
Drug: 5-azacitidine and sargramostim
5-azacitidine will be administered days 1-5 of a 28 day cycle. sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Other Name: Vidaza, GM-CSF

  Eligibility

Ages Eligible for Study:   6 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 6 months
  2. Initial diagnosis of poor -risk AML or MDS (defined in section 3.2), treated with either stem cell transplant or cytarabine-based consolidation chemotherapy, within the past 60-185 days
  3. ECOG performance status 0-2
  4. No morphologic evidence of leukemia or active MDS as determined by JHH Hematopathologist independent review of a bone marrow aspirate and biopsy done following the completion of therapy and within 14 days prior to enrollment
  5. Peripheral blood count recovery: Neutrophil count ≥ 1000 /µL, platelet count ≥ 50x 109 /µL without platelet transfusions, and adequate hematocrit independent of red cell transfusions .
  6. No evidence of extramedullary leukemia, such as CNS or soft tissue involvement
  7. Adequate end organ function as measured by the following: AST and ALT < 4 x normal, total serum bilirubin < 2 x upper limit normal (unless due to hemolysis, Gilbert's syndrome, or ineffective erythropoiesis), creatinine < 2 x upper limit of normal
  8. Ability to give informed consent
  9. In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile

Exclusion Criteria:

  1. Patients with untreated or uncontrolled infections
  2. Patients with untreated or uncontrolled grade 3 or 4 GVHD
  3. Pregnancy and lactation
  4. Concurrent use of any other investigational agents.
  5. Known HIV-positive patients.
  6. Known hypersensitivity to 5AC or GM-CSF
  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: NCT01700673

Contacts
Contact: Margaret Showel, MD 410-614-7059
Contact: Noah Tucker 410-614-7833 ntucker5@jhmi.edu

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Principal Investigator: Margaret Showel, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01700673     History of Changes
Other Study ID Numbers: J1240, P01CA015396, NA_00072223
Study First Received: October 2, 2012
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
maintenance treatment
stem cell transplant
cytarabine-based chemotherapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Azacitidine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014