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

NCT ID: NCT00568633

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2015-12-31

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.

Conditions

Leukemia, Myeloid; Leukemia; Acute Myeloid Leukemia (AML)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Allogeneic HSCT

Intervention Type: PROCEDURE

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)

Intervention Type: DRUG

1.5 mg/kg for 5 days by IV

Cyclosporine (CSP)

Intervention Type: DRUG

6.25 mg/kg twice daily oral

Mycophenolate mofetil (MMF)

Intervention Type: DRUG

15 mg/kg twice daily oral

Total lymphoid irradiation (TLI)

Intervention Type: RADIATION

80 cGy/fraction radiotherapy in 10 fractions.

Methylprednisolone sodium succinate

Intervention Type: DRUG

1.0 mg/kg for 5 days by IV

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

Group Type: ACTIVE_COMPARATOR

Best standard care

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: PROCEDURE

Anti-thymocyte globulin (ATG)

1.5 mg/kg for 5 days by IV

Intervention Type: DRUG

Cyclosporine (CSP)

6.25 mg/kg twice daily oral

Intervention Type: DRUG

Mycophenolate mofetil (MMF)

15 mg/kg twice daily oral

Intervention Type: DRUG

Total lymphoid irradiation (TLI)

80 cGy/fraction radiotherapy in 10 fractions.

Intervention Type: RADIATION

Methylprednisolone sodium succinate

1.0 mg/kg for 5 days by IV

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Hematopoietic stem cell transplantation (HSCT); Peripheral blood stem cell (PBSC) transplantation; Thymoglobulin; Anti-thymocyte globulin (rabbit) (ATG); Ciclosporin; cyclosporin A; cyclosporin; Cellcept; Solumedrol; Medrol; Depo-Medrol; P-Care D40; P-Care D80; Standard of Care (physician discretion); Regular medical care

Eligibility Criteria

Inclusion Criteria

• ≥ 50 years of age and ≤ 75 years of age.
• De novo acute myelogenous leukemia (AML), based on FAB and WHO criteria.
• Intermediate or unfavorable cytogenetic abnormalities based on Southwest Oncology Group (SWOG) Cytogenetic Criteria.
• First morphologic complete remission (CR), or CRp (a complete remission but with low platelets) following 1 or 2 courses of induction therapy, documented no more than 8 weeks prior to the date of enrollment and confirmed at time of enrollment.
• Karnofsky Performance Score ≥ 60.
• Suitable for non-myeloablative transplantation or best treatment.
• Able to understand and willing to sign a written informed consent document.

Exclusion Criteria

• AML with favorable cytogenetic features based on SWOG Cytogenetic Criteria
• AML, either treatment-related or MDS-related
• Active CNS disease as identified by positive CSF cytospin at time of enrollment.
• Prior or concurrent malignancies except localized non-melanoma skin malignancies or treated cervical carcinoma in situ. (EXCEPTION: Cancer treated with curative intent > 5 years previously is allowed. EXCEPTION: Low grade lymphoma is allowed as long as active treatment is not required for control of disease)
• Planned for allogeneic transplant using a full-dose conditioning
• Life expectancy < 1 year due to diseases other than malignancy
• Pregnant or breastfeeding.
• HIV-seropositive.
• Uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month.
• Symptomatic coronary artery disease or uncontrolled congestive heart failure. Left ventricular ejection fraction (LVEF) is not required to be measured, however if measured, exclusion if ejection fraction is < 30%.
• Requiring supplementary continuous oxygen. Diffusing capacity of the lungs for carbon monoxide (DLCO) is not required to be measured, however if it is measured, exclusion if DLCO < 35%.
• Fulminant liver failure
• Cirrhosis with evidence of portal hypertension or bridging fibrosis
• Alcoholic hepatitis
• Esophageal varices
• A history of bleeding esophageal varices
• Hepatic encephalopathy
• Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time
• Ascites related to portal hypertension
• Chronic viral hepatitis with total serum bilirubin > 3 mg/dL
• Symptomatic biliary disease

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Robert Lowsky

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Lowsky

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Kaiser Permanente Northern California

Hayward, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Univeristy of California Davis Medical Center

Sacramento, California, United States

Stanford University School of Medicine

Stanford, California, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

Countries

United States

Other Identifiers

97843

Identifier Type: OTHER

Identifier Source: secondary_id

BMT190

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-05567

Identifier Type: -

Identifier Source: org_study_id