Despite improvements in outcomes after Hematopoietic Cell Transplantation (HCT) for Acute
Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), the risk of relapse remains high
and is the most common cause of mortality after HCT. Moreover, treatment options for relapse
after HCT are limited. Strategies to reduce relapse with maintenance therapy in patients who
are at high risk are needed to improve survival. 5-aza is a hypomethylating agent that has
shown immune modulating properties that may enhance the graft-versus-leukemia (GVL) effect,
including upregulation of tumor-associated antigen and costimulatory molecule expression.
Moreover, 5-aza has properties that suggest protection against graft-versus-host disease
(GVHD) as well. Preliminary data shows that it is well tolerated and effective in clinical
use for the treatment of AML or MDS relapse after HCT, as well as for maintenance therapy.
This study will evaluate the use of 5-aza for maintenance after HCT in patients with AML or
MDS with risk factors that are associated with a high risk for relapse.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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 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
- FLT3 mutation
- Disease status≥CR2 at time of HCT
- Detectable disease at time of HCT
- 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 (CKD) (creatinine must be at baseline
for subjects with CKD)
- 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 CKD (creatinine
must be at baseline for subjects with CKD), 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 CR (including CRi and marrow CR) 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 (CKD) (creatinine must be at baseline
for subjects with CKD)
- 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 CKD (creatinine
must be at baseline for subjects with CKD), 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