Single Arm, Open Label, Phase I Study for Dose and Schedule Finding of Decitabine in Patients With Higher-risk MDS and MDS/AML Receiving Allogeneic Stem Cell Transplantation
18 Years
65 Years
Both
Myelodysplastic Syndrome, Acute Myeloid Leukemia
Trial Information
Single Arm, Open Label, Phase I Study for Dose and Schedule Finding of Decitabine in Patients With Higher-risk MDS and MDS/AML Receiving Allogeneic Stem Cell Transplantation
1. Transplant course
- BMT from an HLA-matched sibling or a suitably matched (up to 2-allele mismatched)
family or unrelated donor will be performed according to the policies of the
institute.
- A preparative regimen will be started 6 days before the day of stem cell infusion
1. Myeloablative-intensity conditioning regimen: FB4+ATG
2. Reduced-intensity conditioning regimen; FB2+ATG
3. Graft-versus-host disease prophylaxis
- Sibling transplant: Cyclosporine and short-course Methotrexate
- Unrelated transplant: Tacrolimus and short-course Methotrexate
- The dose of calcineurin inhibitors (cyclosporine and tacrolimus) will be gradually
tapered from day 60 (for all sibling transplants) or day 90 (for all unrelated
transplants) and discontinued within 2 or 3 months after SCT in the absence of
graft-versus-host disease.
2. Decitabine maintenance course
- For the patients who finish the above transplant procedure and meet the enrollment
criteria, decitabine will be given at a dose of 5mg/m2/day ~ 15mg/m2/day iv over 1
hour for 5 consecutive days. The drug will be repeated every 4 weeks for up to 12
cycles.
- Dose escalation strategy between cohorts and between cycles in the same cohort
patients will be based upon the quantitatively measured hematological toxicity
(e.g., ANC or platelet count at nadir). In other words, a mechanism-based
pharmacokinetic / pharmacodynamic model developed using sparsely sampled patients'
PK data and toxicity response will be used to titrate next cycle doses for the
patients and initial doses for new cohort patients. In other words, a
mechanism-based pharmacokinetic / pharmacodynamic model developed using sparsely
sampled patients' PK data and toxicity response will be used to titrate next cycle
doses for the patients and initial doses for new cohort patients.
Inclusion Criteria
Inclusion Criteria for allogeneic transplantation::
- Patients with a diagnosis of MDS (IPSS intermediate-2 or higher) before allogeneic
transplantation
- HLA-compatible unrelated (HLA-A, -B, -C and -DRB1 matched or with 2 allele mismatch)
- Performance status < ECOG 2
- Acceptable organ function defined as:Serum creatinine < 1.5 times the institutional
ULN,Serum bilirubin < 1.5 times the institutional ULN,AST, ALT and alkaline
phosphatase < 3 times the institutional ULN.
Inclusion Criteria for decitabine maintenance therapy:
- 6 to 10 weeks after alloHSCT
- patients who are confirmed complete remission(CR) within 2 weeks for treatment
start(CR:less than 5% blasts in an aspirate bone marrow sample or no leukemic blasts
in the peripheral blood, no cytogenetic aberrations)
- Performance status < ECOG 2
- Acceptable organ function defined as:Serum creatinine < 1.5 times the institutional
ULN,Serum bilirubin < 1.5 times the institutional ULN,AST, ALT and alkaline
phosphatase < 3 times the institutional ULN.
- Platelet count ≥ 30,000/μL without platelet transfusion for 7 days and ANC ≥ 1,000/μL
without colony stimulating factor support at the time of enrollment
- Written informed consent form
Exclusion Criteria:
- HIV positive
- Active uncontrolled infection
- Pregnancy or breastfeeding
- patients who have residual disease after allo SCT or primary graft failure
- Uncontrolled grade 3- 4 acute GVHD
- patients who are known or suspected hypersensitivity to decitabine
- patient who are not suitable for the trial in accordance with principal
investigator's decision
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose and schedule finding of post-BMT Decitabine Treatment
Outcome Description:
To find the safe dose and schedule of administration of the drug decitabine that can be given to patients with higher risk MDS or secondary AML evolving from MDS who received allogeneic stem cell transplantation
Outcome Time Frame:
For up to 2 years after the start of Decitabine
Safety Issue:
Yes
Principal Investigator
Yoo-Jin Kim, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Division of Hematology,Department of Internal Medicine,Catholic Blood and Marrow Transplantation Center,Seoul St. Mary's Hospital
Authority:
Korea: Food and Drug Administration
Study ID:
DEC-KOR-9007
NCT ID:
NCT01277484
Start Date:
January 2011
Completion Date:
March 2013
Related Keywords:
- Myelodysplastic Syndrome
- Acute Myeloid Leukemia
- decitabine
- dose
- schedule
- safety
- allogeneic stem cell transplantation
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
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