Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
Conditions
Brief summary
Primary: To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT) performed for AML or high-risk MDS.
Detailed description
Secondary: * To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT. * To determine the rates disease relapse, 1-year disease-free survival, and overall survival. * To assess lymphoid and myeloid chimerism while on decitabine maintenance. * To determine the incidence of acute and chronic GVHD. * To assess immunologic reconstitution after alloHSCT. * To assess changes in gene expression and methylation patterns following decitabine treatment * To assess the effects of decitabine on immune reconstitution post transplant. * To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment.
Interventions
DRUGDecitabine
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient Screening Criteria and Enrollment Process This is a single institution study at Washington University School of Medicine in St. Louis. Study population are patients \>=18 years of age, with histologically confirmed AML or MDS according to World Health Organization (WHO) criteria undergoing alloHCST. All screening procedures are part the patients clinical care. * Patients, or their legal authorized representative, will provide written informed consent for the study prior to alloHSCT, or through 100 days following alloHSCT * Patients will undergo alloHSCT as per institutional guidelines. AlloHSCT may be performed using both related and unrelated donors, myeloablative or non-myeloablative preparative regimens, and with either peripheral blood or bone marrow as a source of graft. * Patients who fulfill both the Inclusion Criteria and
Exclusion criteria
in the period of ≥ 50 and ≤ 100 days after alloHSCT will be registered on the study and will receive decitabine maintenance. Bone marrow biopsy will be performed ≤ 14 days prior to starting decitabine to confirm remission. Any GVHD prophylaxis or therapy is allowed during the study. * Patients who do not fulfill Inclusion Criteria are not eligible to be registered on the study and are considered screening failures. * Study will include maximum of 32 evaluable patients. Inclusion Criteria * History of AML or MDS using WHO classification. * \>50 and \<100 days following HLA-matched related or unrelated donor alloHSCT. Donors may be mismatched at single antigen at HLA-A, -B or -DR locus plus possible single antigen mismatch at HLA-C according to institution guidelines. Two-antigen mismatch at a single locus is not allowed. * Age \>=18 years. * Bone marrow biopsy confirming complete remission after alloHSCT o Complete remission: less than 5% blasts in an aspirate bone marrow sample with a count of at least 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease PLUS absolute neutrophil count (ANC) \> 1,500/μL, platelet count ≥ 50,000/μL and no leukemic blasts in the peripheral blood. * Platelet count ≥ 50,000/µL without platelet transfusion for 7 days and ANC ≥ 1,500/µL without colony stimulating factor support. * Performance status \< ECOG 2. * Acceptable organ function defined as: * creatinine \< 1.5 times the institutional ULN or creatinine clearance (calculated by the Cockroft and Gault method) ≥ 30 mL/min * bilirubin \< 1.5 times the institutional ULN * AST, ALT and alkaline phosphatase \< 2.5 times the institutional ULN. * Each Patient or their legal authorized representative must sign an institutional review board/ethics committee-approved informed consent indicating their awareness of the investigational nature of this study. * Female Subjects: * Female of childbearing potential (FCBP\*) must agree to use a reliable form of contraception or to practice complete abstinence from heterosexual intercourse for at least 28 days before starting study drug, while participating in the study, and for at least 28 days after discontinuation from the study. The methods of reliable contraception include intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, partner's vasectomy, latex condom, diaphragm and cervical cap. * FCBP must agree to pregnancy testing. * FCBP must a negative pregnancy test prior to starting study drug. * FCBP must agree to abstain from donating blood and/or egg during study participation and for at least 28 days after discontinuation from the study \* A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months). * Male Subjects: * Must agree to use a latex condom during sexual contact with FCBP while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy * Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from the study. * Must agree that if a pregnancy or a positive pregnancy test does occur in a female partner of a male study subject during study participation, study drug must be immediately discontinued and must immediately notify the principal investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose and schedule of decitabine when administered as maintenance therapy after alloHSCT performed for AML or high-risk MDS. | Up to 6 weeks (completion of first cycle) |
Secondary
| Measure | Time frame |
|---|---|
| To determine the rates disease relapse | Every 3 months for 2 years then every 6 months for 3 years |
| To assess lymphoid and myeloid chimerism while on decitabine maintenance. | End of cycle 3 (18 weeks) |
| To determine the incidence of acute GVHD. | End of study (42 weeks) |
| To assess immunologic reconstitution after alloHSCT. | End of study (42 weeks) |
| To assess changes in gene expression and methylation patterns following decitabine treatment | End of study (42 weeks) |
| To determine the safety and tolerability of decitabine as maintenance therapy after alloHSCT. | Up to 30 days after end of study (approximately 46 weeks) |
| To access the frequency of FoxP3+ CD3+/CD4+ and CD3+/CD8+ lymphocytes before and after decitabine treatment. | End of cycle 3 (18 weeks) |
| To determine the 1-year disease-free survival | 1 year |
| To determine overall survival. | Every 3 months for 2 years then every 6 months for 3 years |
| To determine the incidence of chronic GVHD. | End of study (42 weeks) |
| To assess the effects of decitabine on immune reconstitution post transplant. | End of study (42 weeks) |
Countries
United States
Outcome results
None listed