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

Study Overview
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Brief Summary
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To determine the impact of maintenance therapy in patients with MDS/AML in remission.

Detailed Description
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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.

Official Title
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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)

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Azacitidine
* Biological: Sargramostim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 6 months 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 ECOG performance status 0-2 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 Peripheral blood count recovery: Neutrophil count ≥ 1000 /µL, platelet count ≥ 50x 109 /µL without platelet transfusions, and adequate hematocrit independent of red cell transfusions . No evidence of extramedullary leukemia, such as CNS or soft tissue involvement 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 Ability to give informed consent 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: Patients with untreated or uncontrolled infections Patients with untreated or uncontrolled grade 3 or 4 GVHD Pregnancy and lactation Concurrent use of any other investigational agents. Known HIV-positive patients. Known hypersensitivity to 5AC or GM-CSF

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Myeloablative BMT<br>Azacitidine and sargramostim after myeloablative stem cell transplant | Drug: Azacitidine<br>* Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.<br>* Other names: Azacytidine;Biological: Sargramostim<br>* Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.<br>* Other names: GM-CSF;|
| Experimental: Non-myeloablative BMT<br>Azacitidine and sargramostim after non-myeloablative stem cell transplant | Drug: Azacitidine<br>* Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.<br>* Other names: Azacytidine;Biological: Sargramostim<br>* Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.<br>* Other names: GM-CSF;|
| Experimental: Standard consolidation<br>Azacitidine and sargramostim after standard consolidation | Drug: Azacitidine<br>* Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.<br>* Other names: Azacytidine;Biological: Sargramostim<br>* Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.<br>* Other names: GM-CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-year Relapse Free Survival of Patients | 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 sargramostim (GM-CSF) during remission, following definitive therapy with either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy. | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic Toxicity as Determined by Anemia | Percentage of patients with anemia, the most commonly reported hematologic toxicity, after receiving the combination of Azacitidine and sargramostim | 1 year | 
| One-year RFS | We will report the number of participants with one year RFS | 1 year | 
| Overall Survival | Percentage of participants with overall survival at 2 years. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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maintenance treatment, stem cell transplant, cytarabine-based chemotherapy