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
|ClinicalTrials.gov Identifier: NCT00253513|
Recruitment Status : Completed
First Posted : November 15, 2005
Results First Posted : February 11, 2011
Last Update Posted : June 1, 2012
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndromes||Drug: fludarabine Drug: treosulfan Procedure: allogeneic blood or bone marrow transplantation||Phase 1 Phase 2|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia|
|Study Start Date :||June 2005|
|Actual Primary Completion Date :||October 2009|
|Actual Study Completion Date :||October 2009|
- Drug: fludarabine
30 mg/m2, IV for 5 days
- Drug: treosulfan
12 or 14 g/m2, IV for 5 days
- Procedure: allogeneic blood or bone marrow transplantation
bone marrow or peripheral blood stem cells
- Number of Patients Experiencing Regimen-related Toxicity Events in Study Population [ Time Frame: 34 days and 2 years ]Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal
- Number of Patients Experiencing Graft Failure [ Time Frame: 42 days ]Graft versus Host Disease (GVHD) is a frequent complication of allogeneic bone marrow transplant in which the engrafted donor cells attacks the patient's organs and tissue. Acute GVHD (aGVHD) usually occurs during the first three months following an allogeneic BMT. Chronic GVHD (cGVHD) usually develops after the third month post-transplant. Patients may experience one, both or neither.
- Incidence (Percent of Participants) With Nonrelapse Mortality (NRM) by Day 200 (Secondary Phase Only) [ Time Frame: 200 days ]NRM (Non relapse mortality) - death not attributed to the primary cancer.
- Number of Subjects Who Are Without Disease at One Year as Indicator of Disease Free Survival. [ Time Frame: One year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00253513
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239-3098|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109-1023|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Eneida Nemecek, MD||OHSU Knight Cancer Institute|