A California Cooperative Clinical Study Comparing Allogeneic Hematopoietic Cell Transplantation Using Nonmyeloablative Host Conditioning With Total Lymphoid Irradiation and Anti-thymocyte Globulin Versus Best Standard of Care in Acute Myeloid Leukemia (AML) in First Complete Remission
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Stanford University
- Enrollment
- 58
- Locations
- 5
- Primary Endpoint
- Overall Survival (OS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 50 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Allo-HSCT + TLI + 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
Intervention: Allogeneic HSCT (Procedure)
Allo-HSCT + TLI + 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
Intervention: Anti-thymocyte globulin (ATG) (Drug)
Allo-HSCT + TLI + 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
Intervention: Cyclosporine (CSP) (Drug)
Allo-HSCT + TLI + 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
Intervention: Mycophenolate mofetil (MMF) (Drug)
Allo-HSCT + TLI + 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
Intervention: Total lymphoid irradiation (TLI) (Radiation)
Allo-HSCT + TLI + 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
Intervention: Methylprednisolone sodium succinate (Drug)
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
Intervention: Best standard care (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: 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 Outcomes
- Early Graft Loss(2 years)
- Disease-free Survival (DFS)(2 years)
- Non-relapse Mortality(2 years)
- Complete Donor Hematopoietic Cell Chimerism(2 years)
- Patients Completing the Intended Therapy in Both Arms(2 years)
- Relapse Rate(2 years)
- Transplant-related Mortality(100 days and 6 months)
Investigators
Robert Lowsky
Professor of Medicine
Stanford University