Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
Decitabine, Dacogen, Filgrastim, G-CSF, Neupogen, Cyclosporine, Sandimmune, CYA, Cyclosporin A, Peripheral blood stem cells, PBSC, Allogeneic bone marrow transplantation, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, previously treated myelodysplastic syndromes, childhood myelodysplastic syndromes
Brief summary
RATIONALE: Peripheral stem cell transplantation may be an effective treatment for leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia that has relapsed following bone marrow transplantation. PURPOSE: Phase I/II trial to study the effectiveness of decitabine and peripheral stem cell transplantation in treating patients who have leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia that has relapsed after bone marrow transplantation.
Detailed description
OBJECTIVES: I. Determine the maximum tolerated dose of decitabine in patients with relapse post allogenic bone marrow transplant. II. Determine the toxicity of decitabine combined with filgrastim (G-CSF) primed allogeneic peripheral blood stem cells in patients who relapsed within 1 year after allogeneic bone marrow transplantation. III. Determine the effectiveness in reinducing remission in these patients. OUTLINE: Patients receive decitabine IV for 6 hours every 12 hr for 5 days. Peripheral blood stem cells (PBSC) are administered 5 days after last dose of decitabine. Donors receive filgrastim subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to first PBSC collection. If insufficient number of cells are collected, bone marrow can be harvested for supplementation. Donor cells should be collected prior to decitabine infusion. Patients receive filgrastim SQ administered daily starting 1 day after PBSC infusion until blood counts recover. For GVHD prophylaxis, patients receive cyclosporine IV daily on day -2, then orally once dose is tolerable. Dose of decitabine is escalated in cohorts of 3-6 patients. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then that dose is declared the maximum tolerated dose. Patients are followed weekly. If none of the first 5 patients survive in remission for more than 100 days, the study will be terminated. PROJECTED ACCRUAL: At least 15 patients will be accrued for this study over 2 years.
Interventions
BIOLOGICALFilgrastim
Subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to first PBSC collection then daily starting 1 day after PBSC infusion until blood counts recover.
DRUGCyclosporine
IV daily on day -2, then orally once dose is tolerable, dose may be escalated.
DRUGDecitabine
IV for 6 hours every 12 hr for 5 days.
PROCEDUREAllogeneic Bone Marrow Transplantation
Stem cell infusion on Day 0.
PROCEDUREPeripheral Blood Stem Cell Transplantation
Peripheral blood stem cells (PBSC) are administered 5 days after last dose of decitabine.
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Acute leukemia, myelodysplastic syndromes or chronic myelogenous leukemia (CML) in accelerated phase or blast crisis and relapsed within 1 year after allogeneic bone marrow transplantation Must not be candidates for second course of high dose chemoradiotherapy PATIENT CHARACTERISTICS: Age: 60 and under Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 3 mg/dL Renal: Creatinine less than 2 mg/dL Cardiovascular: Greater than 40% ejection fraction per MUGA scan or ECHO Other: Not pregnant No serious intercurrent illness No active CNS disease Must be ineligible for protocols of higher priority No active acute graft vs host disease (GVHD) greater than grade 2 or extensive chronic GVHD No active uncontrolled infection Original marrow donor must undergo filgrastim primed peripheral blood stem cell collection PRIOR CONCURRENT THERAPY: See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) Decitabine | Weekly for 1 year |
Countries
United States
Outcome results
None listed