Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission
- Conditions
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic SyndromeAdult Acute Myeloid Leukemia in Remission
- Interventions
- Biological: filgrastimBiological: Anti-Thymocyte GlobulinProcedure: Allogeneic Hematopoietic Stem Cell Transplantation
- Registration Number
- NCT00070135
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This phase II trial studies how well fludarabine and busulfan followed by a donor (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia that is in first complete remission. Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stops the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus, methotrexate, and rabbit antithymocyte globulin before or after the transplant may stop this from happening.
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine if allogeneic transplantation from a matched sibling or unrelated donor using a non-myeloablative preparative regimen results in a 2-year disease-free survival (DFS) that is better than historical results using standard chemotherapy.
SECONDARY OBJECTIVES:
I. Determine 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host (GVHD) disease and relapse among patients with acute myeloid leukemia (AML) in first complete remission (CR1) following a non-myeloablative preparative regimen.
II. To examine recovery of T and B cell number and function following non-myeloablative stem cell transplant.
III. To examine the time course of T, B and myeloid progenitor chimerism following this preparative regimen.
IV. To characterize the pharmacokinetics of intravenous busulfan used in a non-myeloablative preparation regimen in AML patients age \>= 60 years.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (IV) over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.
GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV twice daily (BID) on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.
ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRASNPLANTATION (PBSC): Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim subcutaneously (SC) daily beginning on day 12 and continuing until blood counts recover.
Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (fludarabine, busulfan, allogeneic PBSC) filgrastim PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover. Treatment (fludarabine, busulfan, allogeneic PBSC) Anti-Thymocyte Globulin PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover. Treatment (fludarabine, busulfan, allogeneic PBSC) Allogeneic Hematopoietic Stem Cell Transplantation PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover. Treatment (fludarabine, busulfan, allogeneic PBSC) busulfan PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover. Treatment (fludarabine, busulfan, allogeneic PBSC) methotrexate PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover. Treatment (fludarabine, busulfan, allogeneic PBSC) fludarabine phosphate PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover. Treatment (fludarabine, busulfan, allogeneic PBSC) tacrolimus PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3. GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2. ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover.
- Primary Outcome Measures
Name Time Method 2 Year Disease Free Survival In Unrelated Donor Recipient Group 2 years Percentage of participants who were alive and relapse free at 2 years for patients who were matched with an unrelated donor for transplant. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
A relapse is defined as any of the following:
* Reappearance of leukemia blasts cells in peripheral blood
* \>5% blasts in the marrow, not attributable to another cause (e.g., bone marrow regeneration)
* If there are no circulating blasts, but the marrow contains 5-20% blasts, a repeat bone marrow ≥ 1 week later with \>5% blasts is necessary to meet the criteria for relapse
* The development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid
- Secondary Outcome Measures
Name Time Method Non-relapse Mortality (NRM) Up to 5 years Percentage of patients who died due to causes other than relapse
2 Year DFS for All Patients Up to 2 years Percentage of participants who were alive and relapse free at 2 years for all patients. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
Trial Locations
- Locations (21)
New York Weill Cornell Cancer Center at Cornell University
🇺🇸New York, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Greenebaum Cancer Center at University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Monter Cancer Center of the North Shore-LIJ Health System
🇺🇸Lake Success, New York, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital
🇺🇸Manhasset, New York, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Dana-Farber/Brigham and Women's Cancer Center
🇺🇸Boston, Massachusetts, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
CCOP - North Shore University Hospital
🇺🇸Manhasset, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States