Neoplasms

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Leukemia

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Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

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Acute Graft Versus Host Disease

Anti-Infective Agents

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Anti-Inflammatory Agents

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Cytarabine

Cyclosporine

Cyclosporins

Prednisolone

Mycophenolic Acid

Thymoglobulin

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Antilymphocyte Serum

Enzyme Inhibitors

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Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

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

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

Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and \< 7 x 10e8 CD3+ cells/kg.

Allogeneic HSCT

Anti-thymocyte globulin (ATG)

Cyclosporine (CSP)

Mycophenolate mofetil (MMF)

80 cGy/fraction radiotherapy in 10 fractions.

Total lymphoid irradiation (TLI)

Methylprednisolone sodium succinate

Intervention consist of:

* 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

Best standard care

Robert Lowsky

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.

Treatment assignment was based on availability of an HLA-matched donor.

Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML

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

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).

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 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).

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 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).

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.

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.

The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion

Genzyme, a Sanofi Company

Stanford University

Professor of Medicine

Non-serious adverse events were not collected in this study.

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

Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and \< 7 x 10e8 CD3+ cells/kg.

Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV

Cyclosporine (CSP): 6.25 mg/kg twice daily oral

Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral

Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions.

Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV

Allo-HSCT + TLI + ATG

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

Best standard care: Intervention consist of:

* 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

Best Standard Care

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Robert Lowsky, Professor of Medicine (Blood and Marrow Transplantation)

Overall Survival (OS)

Disease-free Survival (DFS)

Non-relapse Mortality

Relapse Rate

At 100 days

At 6 months

Participants in the Best Standard Care arm did not receive transplant, and are not evaluable for transplant outcomes.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML	NCT00568633	Leukemia, Myelo... Leukemia Acute Myeloid L...	Allogeneic HSCT Anti-thymocyte ... Cyclosporine (C... Mycophenolate m... Total lymphoid ... Methylprednisol... Best standard c...	50 Years - 75 Years	Stanford University
Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML	NCT00568633	Leukemia, Myelo... Leukemia Acute Myeloid L...	Allogeneic HSCT Anti-thymocyte ... Cyclosporine (C... Mycophenolate m... Total lymphoid ... Methylprednisol... Best standard c...	50 Years - 75 Years	Stanford University

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