Acute Myeloid Leukemia Clinical Trial
Treosulfan and Fludarabine in Treating Younger Patients Who Are Undergoing a Donor Stem Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
Summary
RATIONALE: Drugs used in chemotherapy, such as treosulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving treosulfan and fludarabine together with a donor bone marrow transplant or a peripheral stem cell transplant may be an effective treatment for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
PURPOSE: This phase II trial is studying giving treosulfan together with fludarabine to see how well it works in treating patients who are undergoing a donor stem cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.
Full Description
OBJECTIVES:
Primary Phase
Determine the best dose of treosulfan when administered with fludarabine as a reduced-intensity conditioning regimen followed by allogeneic hematopoietic stem cell transplantation, in terms of incidence of severe to fatal toxicity to major organ systems and incidence of graft failure, in patients with acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome.
Secondary Phase
Determine the safety of this regimen, in terms of incidence of grade II-IV acute and chronic graft-versus-host disease, in these patients.
Determine, preliminarily, the efficacy of this regimen, in terms of incidence of relapse, overall and disease-free survival, donor chimerism on days 28 and 100, and incidence of 200-day and 1-year nonrelapse mortality, in these patients.
Determine the pharmacokinetic and pharmacodynamic profile of treosulfan in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-finding study of treosulfan.
Reduced-intensity conditioning: Patients receive treosulfan IV over 2 hours on days -6 to -4 and fludarabine IV over 30 minutes on days -6 to -2.
Cohorts of 5-10 patients receive escalating/de-escalating doses of treosulfan until the best dose is determined among the 3 pre-selected doses. The best dose is defined as the dose preceding that at which 4 of 10 patients experience dose-limiting toxicity.
Allogeneic hematopoietic cell transplantation (AHCT): Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
All male patients with acute lymphoblastic leukemia OR male patients with acute myeloid leukemia who have prior or current testicular involvement receive external-beam radiotherapy to the testicles before AHCT.
After completion of study treatment, patents are followed periodically.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome
Any phase allowed, including any of the following:
Disease in remission
Relapsed or primary refractory disease
No CNS leukemic involvement not clearing with prior intrathecal chemotherapy and/or cranial radiotherapy
Planning to undergo unmanipulated allogeneic bone marrow or peripheral blood stem cell transplantation
Filgrastim (G-CSF) mobilization of bone marrow or stem cells allowed
Donor available, meeting 1 of the following criteria:
HLA-identical related donor
HLA-A, -B, -C, -DRB1, and -DQB1 matched unrelated donor by high-resolution DNA typing
A single allele mismatch allowed
PATIENT CHARACTERISTICS:
Performance status
Karnofsky 70-100% OR
Lansky 70-100%
Life expectancy
Not specified
Hematopoietic
Not specified
Hepatic
Bilirubin ≤ 2 times upper limit of normal (ULN)
AST ≤ 2 times ULN
No evidence of synthetic dysfunction
No severe cirrhosis
No active infectious hepatitis
Renal
Creatinine clearance ≥ 50%
Creatinine ≤ 2 times ULN
Dialysis independent
Cardiovascular
No cardiac insufficiency requiring treatment
No symptomatic coronary artery disease
Ejection fraction ≥ 35% (for patients with history of cardiac disease or anthracycline exposure)
Pulmonary
PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR
PO_2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
Not requiring supplementary continuous oxygen
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other disease that would severely limit life expectancy
No HIV positivity
No active infection requiring deferral of conditioning
No known hypersensitivity to the study drugs
PRIOR CONCURRENT THERAPY:
Biologic therapy
See Disease Characteristics
No prior allogeneic bone marrow or stem cell transplantation
No concurrent umbilical cord blood or autologous transplantation
Chemotherapy
See Disease Characteristics
Radiotherapy
See Disease Characteristics
Other
More than 4 weeks since prior experimental drugs
Concurrent enrollment on another protocol for graft-versus-host disease prophylaxis allowed
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There are 2 Locations for this study
Portland Oregon, 97239, United States
Seattle Washington, 98109, United States
Seattle Washington, 98109, United States
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