Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation From HLA Matched Related Donors for Treatment of Older Patients With De Novo or Secondary Acute Myeloid Leukemia in First Complete Remission
Overview
- Phase
- Phase 2
- Intervention
- nonmyeloablative allogeneic hematopoietic stem cell transplantation
- Conditions
- Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
- Sponsor
- Fred Hutchinson Cancer Center
- Enrollment
- 17
- Locations
- 2
- Primary Endpoint
- Disease-free Survival-incidence of Survival Without Relapse
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This phase II trial studies how well reduced intensity donor peripheral blood stem cell (PBSC) transplant works in treating patients with de novo or secondary acute myeloid leukemia (AML) in remission. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening
Detailed Description
PRIMARY OBJECTIVES: I. To determine if a one-year disease free survival of \>= 35% can be achieved among patients \>= 55 years old with de novo and secondary AML in first complete remission (CR1) who undergo nonmyeloablative hematopoietic stem cell transplant (HSCT) from human leukocyte antigen (HLA) identical related donors. II. To determine if a day +200 nonrelapse related mortality of \< 15% can be achieved among patients \>= 55 years old with de novo and secondary AML in CR1 who undergo nonmyeloablative HSCT from HLA identical related donors. OUTLINE: CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine (CSP) orally (PO) twice daily (BID) on days -3 to 56 with taper to day 77. Patients also receive mycophenolate mofetil (MMF) PO BID on days 0-27. After completion of study treatment, patients are followed up on days 28, 56, and 84; months 6, 12, 18, and 24; and then yearly for 5 years.
Investigators
Brenda Sandmaier
Principal Investigator
Fred Hutchinson Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Patients with de novo AML (French-American-British \[FAB\] MO-M2, M4-M7) or secondary AML who achieve CR1 after induction chemotherapy and one or two cycles of consolidation chemotherapy
- •Transplant conditioning must occur within 6 months of diagnosis
- •Patient enrollment must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI) or the PI's designee
- •DONOR: Related donor who is genotypically or phenotypically identical
- •DONOR: Age \>= 12 years
- •DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
- •DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
Exclusion Criteria
- •AML FAB M3
- •AML involvement of the central nervous system (CNS) as defined by a positive cytospin of cerebral spinal fluid at the time of enrollment
- •Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology
- •Human immunodeficiency virus (HIV) seropositivity
- •Fungal infections with radiographic progression after receipt of amphotericin B or active triazole for greater than one month
- •Diffusion capacity of carbon monoxide (DLCO) corrected \< 40%
- •Total lung capacity (TLC) \< 40%
- •Forced expiratory volume in one second (FEV1) \< 40% or requiring supplementary oxygen
- •The FHCRC principal investigator of the study must approve enrollment of all patients with pulmonary nodules
- •Cardiac ejection fraction \< 40%
Arms & Interventions
Treatment (nonmyeloablative donor PBSC transplant)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Intervention: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Treatment (nonmyeloablative donor PBSC transplant)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Intervention: fludarabine phosphate
Treatment (nonmyeloablative donor PBSC transplant)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Intervention: total-body irradiation
Treatment (nonmyeloablative donor PBSC transplant)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Intervention: cyclosporine
Treatment (nonmyeloablative donor PBSC transplant)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Intervention: mycophenolate mofetil
Treatment (nonmyeloablative donor PBSC transplant)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Intervention: peripheral blood stem cell transplantation
Outcomes
Primary Outcomes
Disease-free Survival-incidence of Survival Without Relapse
Time Frame: By 1 year after transplant
Sufficient evidence will be taken to be an observed rate of DFS at one year after transplant that corresponds to a one-sided 95% confidence interval with an upper limit lower than 35%.
Nonrelapse Mortality (NRM)-Incidence of Nonrelapse Death
Time Frame: 200 days after transplant
Defined as death without morphologic evidence of disease. Sufficient evidence will be taken to be an observed rate of NRM within 200 days of transplant that corresponds to a one-sided 80% confidence interval with a lower limit greater than 15%.
Secondary Outcomes
- Incidence of Rejection(By 1 year after transplant)
- Overall Survival(By 1 year after transplant)
- Incidence of Relapse(By 1 year after transplant)
- Incidence of Acute and Chronic GVHD(aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.)