Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
- Conditions
- Leukemia, MyeloidLeukemiaAcute Myeloid Leukemia (AML)
- Interventions
- Procedure: Allogeneic HSCTDrug: Best standard careDrug: Anti-thymocyte globulin (ATG)Radiation: Total lymphoid irradiation (TLI)
- Registration Number
- NCT00568633
- Lead Sponsor
- Stanford University
- Brief Summary
Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 58
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Allo-HSCT + TLI + ATG Allogeneic HSCT Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 Allo-HSCT + TLI + ATG Anti-thymocyte globulin (ATG) Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 Allo-HSCT + TLI + ATG Cyclosporine (CSP) Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 Allo-HSCT + TLI + ATG Mycophenolate mofetil (MMF) Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 Allo-HSCT + TLI + ATG Total lymphoid irradiation (TLI) Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 Allo-HSCT + TLI + ATG Methylprednisolone sodium succinate Participants achieving complete remission after consolidation therapy \& who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: * Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) * Anti-thymocyte globulin (ATG) Days -11 to -7 * Methylprednisolone Days -11 to -7 * Cyclosporine (CSP) Days -4 to +2 * 5+ of 6 HLA-matched CD34+ cells on Day 0 * Mycophenolate mofetil (MMF), Day 0 to Day +28 Best Standard Care Best standard care Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: * Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) * Autologous transplantation * Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning * Umbilical cord blood transplantation * Haploidentical transplantation
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 2 years Overall survival defined as the time interval between the date of attaining a first complete remission (CR) and the date of death from any cause. The outcome is reported as the number of participants alive (without dispersion).
- Secondary Outcome Measures
Name Time Method Early Graft Loss 2 years Early graft loss means a failure to achieve donor T-cell chimerism of \> 5% at any time after transplant. The outcome is reported as the percentage of participants that experience early graft loss, a number without dispersion.
Disease-free Survival (DFS) 2 years Disease-free survival is defined as the time interval between the date of attaining a first complete remission (CR) and the date of relapse. Disease free survival (DFS) will compared to conventional therapy vs Non-myeloablative Host Conditioning (NMA HCT). The outcome is reported as the number of participants which never experienced disease relapse (without dispersion).
Non-relapse Mortality 2 years Non-relapse mortality is defined as death that occurs after therapy, from any cause except a cause associated with relapse. This will be reported as the number of participants experiencing non-relapse mortality (a number without dispersion).
Complete Donor Hematopoietic Cell Chimerism 2 years Complete donor hematopoietic cell chimerism was evaluated in transplant recipients. Complete donor chimerism will be assessed as the presence of \> 95% donor T-cells (CD3+) in the blood. The outcome is reported as the percentage of participants that achieve complete donor chimerism, a number without dispersion.
Patients Completing the Intended Therapy in Both Arms 2 years The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion
Relapse Rate 2 years Relapse will be determined as ≥ 5% blast cells in the bone marrow, not secondary to regeneration after myelosuppressive therapy; OR emergence of extramedullary leukemia; OR the re-emergence of blasts in the peripheral blood. The outcome will be reported as the number and percentage of participants that meet these criteria (a number without dispersion).
Transplant-related Mortality 100 days and 6 months Transplant-related mortality will be assessed as any death occurring within 6 months post-transplant, from any cause except relapse. It will be measured at 100 day and 6 months after transplant. The outcome is expressed as at the number of participants experiencing transplant-related mortality (a number without dispersion).
Trial Locations
- Locations (5)
Kaiser Permanente Northern California
🇺🇸Hayward, California, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Univeristy of California Davis Medical Center
🇺🇸Sacramento, California, United States
West Virginia University Hospital
🇺🇸Morgantown, West Virginia, United States