Phase II Study of Azacitidine and Sargramostim as Maintenance Treatment for Poor-Risk AML or MDS

• ClinicalTrials.gov Identifier: NCT01700673
• Recruitment Status: Completed
• First Posted: October 4, 2012
• Last Update Posted: October 5, 2020
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description

Brief Summary:

To determine the impact of maintenance therapy in patients with MDS/AML in remission.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia; Myelodysplastic Syndrome	Drug: Azacitidine; Biological: Sargramostim	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Actual Study Start Date: June 2013
• Actual Primary Completion Date: June 2020
• Actual Study Completion Date: June 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Myeloablative BMT; Azacitidine and sargramostim after myeloablative stem cell transplant	Drug: Azacitidine; Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: Vidaza; 5-azacytidine; Azacytidine; Biological: Sargramostim; Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Name: GM-CSF
Experimental: Non-myeloablative BMT; Azacitidine and sargramostim after non-myeloablative stem cell transplant	Drug: Azacitidine; Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: Vidaza; 5-azacytidine; Azacytidine; Biological: Sargramostim; Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Name: GM-CSF
Experimental: Standard consolidation; Azacitidine and sargramostim after standard consolidation	Drug: Azacitidine; Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Names: Vidaza; 5-azacytidine; Azacytidine; Biological: Sargramostim; Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.; Other Name: GM-CSF

Outcome Measures

Primary Outcome Measures :

1. To evaluate the 2 year relapse free survival of patients [ Time Frame: 2 year ]
   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. 1. Describe and quantify the toxicity profile of the combination of 5AC and GM-CSF [ Time Frame: 1 year ]
   1. Describe and quantify the toxicity profile of the combination of 5AC and GM-CSF
2. 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 ]
   2. Determine the impact on one-year RFS and overall survival for poor-risk myeloid disorders following maintenance therapy with 5AC and GM-CSF

Eligibility Criteria

• Ages Eligible for Study: 6 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Maryland

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

National Cancer Institute (NCI)

Investigators

• Study Chair: Margaret Showel, MD; JHU

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01700673
• Other Study ID Numbers: J1240; P01CA015396 ( U.S. NIH Grant/Contract ); NA_00072223 ( Other Identifier: JHMIRB )
• First Posted: October 4, 2012
• Last Update Posted: October 5, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

maintenance treatment; stem cell transplant; cytarabine-based chemotherapy

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Azacitidine; Sargramostim; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors; Immunologic Factors; Physiological Effects of Drugs