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 May 2016 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01700673
First received: October 2, 2012
Last updated: May 23, 2016
Last verified: May 2016
  Purpose
To determine the impact of maintenance therapy in patients with MDS/AML in remission.

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 2019
Estimated Primary Completion Date: October 2017 (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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Months to 100 Years   (Child, Adult, Senior)
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
National Cancer Institute (NCI)
Investigators
Study Chair: Margaret Showel, MD JHU
  More Information

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: May 23, 2016
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
Syndrome
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2016