Azacitidine in Treating Patients With Relapsed Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

Study Overview
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Brief Summary
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This phase II trial studies how well azacitidine works in treating patients with relapsed myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who have undergone stem cell transplant. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Detailed Description
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PRIMARY OBJECTIVES: I. To improve overall survival in patients with post-transplant relapse of myeloid malignancies. OUTLINE: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Official Title
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Treatment of Post-Transplant Relapse and Persistent Disease in Patients With MDS, CMML and AML With Azacitidine

Conditions
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Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Childhood Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: azacitidine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MDS, CMML or AML patients (as diagnosed by World Health Organization [WHO] criteria) with evidence of relapse or progression at >= day 28 and < day 100 post-transplant Recurrent or increased cytogenetic abnormalities by standard karyotype or fluorescence in situ hybridization (FISH) (the cytogenetic abnormalities must have been previously documented at some time point between diagnosis and date of stem cell transplant) Morphologic evidence of recurrence or increased abnormal myeloblasts in peripheral blood or marrow Flow Cytometric evidence of disease as determined by recurrent or increased abnormal myeloblasts in peripheral blood or marrow Extramedullary relapse (local radiotherapy will be allowed) MDS, CMML, or AML patients with persistent stable disease or persistent disease with regression at >= day 28 and < day 100 post-transplant; the inclusion of patients with persistent stable or persistent regressing disease in this protocol is not meant to advocate treatment; however, if the attending physician is inclined to offer treatment then these patients would be eligible for this study Persistence of cytogenetic abnormalities by standard karyotype or FISH Persistent morphologic evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow Persistent flow cytometric evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow Extramedullary persistence or regression Exclusion Criteria: Refractory disease at time of stem cell transplant; patients who received chemotherapy prior to transplant with no evidence of response by International Working Group (IWG) criteria >= 10% bone marrow myeloblasts as measured by morphology Evidence of central nervous system (CNS) disease at time of relapse by morphology or flow (a diagnostic lumbar puncture [LP] is not required at time of relapse) Serum creatinine > 2 x ULN (upper limit of normal) Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2x ULN Performance status > 2 (Eastern Cooperative Oncology Group [ECOG] Scale) Patients with severe disease other than MDS, CMML or AML which would be expected to prevent compliance with treatment Patients with severe infections (pneumonia, sepsis, etc) within the 2 weeks prior to the anticipated start of protocol treatment
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy)<br>Patients receive azacitidine SC or IV on days 1-7. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: azacitidine<br>* Given SC or IV<br>* Other names: Vidaza;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Count of surviving participants at 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Response by IWG Criteria | Count of participants achieving a complete or partial remission at 6 months. | 6 months | 
| Incidence of Grades II-IV Graft-versus-host Disease (GVHD) |  | 6 months |