Phase II Study of 5-azacytidine Maintenance After Transplant for AML or MDS (UPCI 13-165)

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), allogeneic, 5-azacytidine (5-aza), hematopoietic, transplantation, transplant, graft-versus-tumor, graft-versus-host disease (GVHD), epigenetic, maintenance, hypomethylation, relapse Read More

Inclusion Criteria:

• Age≥18 with MDS or high-risk AML, morphologically confirmed and based on World Health Organization criteria (see below for definition of high-risk AML)*, who are transplant candidates with an available human leukocyte antigen (HLA) -matched sibling or unrelated donor with at least 8/8 match

  *Definition of high-risk AML:

• Age≥60 years

• Age<60 years with any of the following:

  • Secondary AML
  • Poor risk cytogenetics, which include abnormalities of chromosome 3, 5, or 7, trisomy 8, 11q23 abnormalities, t(6;9), 20q-, and complex karyotype
  • Fms-like tyrosine kinase 3 (FLT3) mutation
  • Disease status ≥ second complete remission (CR2) at time of HCT
  • Detectable disease at time of HCT
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate major organ function, as defined by AST and ALT < 2 x upper limit of normal, total serum bilirubin < 2 x upper limit of normal (unless due to hemolysis or Gilbert's syndrome, then no upper limit), creatinine < 2 x upper limit of normal, unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease)
• 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:

• Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
• Serum creatinine > 2 x upper limit of normal, unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease), aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin > 2x upper limit of normal
• History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
• Patient may not be receiving any other antineoplastic agents
• Pregnancy
• Concurrent use of any other investigational agents on a clinical trial
• Prior allogeneic stem cell transplant
• Known hypersensitivity to 5-azacytidine * Prior treatment with 5-azacytidine is allowed

Post-transplant eligibility and exclusion criteria

Patients will have to meet the following post-transplant eligibility criteria to initiate treatment:

• In complete response (including complete remission with incomplete blood count recovery and marrow complete response) on bone marrow biopsy for response assessment after HCT (typically day +30)
• Patient is within 30-100 days after HCT
• Absolute neutrophil count (ANC) ≥ 1000/µL, platelet count ≥ 20,000/µL
• ECOG performance status 0-2
• Adequate major organ function, as defined by AST and ALT < 2 x upper limit of normal, total serum bilirubin < 2 x upper limit of normal (unless due to hemolysis or Gilbert's syndrome, then no upper limit), creatinine < 2 x upper limit of normal unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease)
• 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

Patients may not have any of the following post-transplant exclusion criteria:

• Active grade II-IV acute GVHD, for example requiring treatment with steroids at a dose equivalent to prednisone 1mg/kg daily or higher
• Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
• Serum creatinine > 2 x upper limit of normal unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease), aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin > 2x upper limit of normal
• History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
• Pregnancy
• Concurrent use of any other investigational agents on a clinical trial
• Known hypersensitivity to 5-azacytidine * Prior treatment with 5-azacytidine is allowed