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

NCT00568633 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: IRB-0556797843BMT190
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

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)

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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).

  2 years

Secondary Outcomes (7)

• Disease-free Survival (DFS)

  2 years

• Non-relapse Mortality

  2 years

• Relapse Rate

  2 years

• Transplant-related Mortality

  100 days and 6 months

• Complete Donor Hematopoietic Cell Chimerism

  2 years

Study Arms (2)

Allo-HSCT + TLI + ATG

EXPERIMENTAL

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

Procedure: Allogeneic HSCT; Drug: Anti-thymocyte globulin (ATG); Drug: Cyclosporine (CSP); Drug: Mycophenolate mofetil (MMF); Radiation: Total lymphoid irradiation (TLI); Drug: Methylprednisolone sodium succinate

Best Standard Care

ACTIVE COMPARATOR

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

Drug: Best standard care

Interventions

Allogeneic HSCT 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.

Also known as: Hematopoietic stem cell transplantation (HSCT), Peripheral blood stem cell (PBSC) transplantation

Allo-HSCT + TLI + ATG

Anti-thymocyte globulin (ATG) DRUG

1.5 mg/kg for 5 days by IV

Also known as: Thymoglobulin, Anti-thymocyte globulin (rabbit) (ATG)

Allo-HSCT + TLI + ATG

Cyclosporine (CSP) DRUG

6.25 mg/kg twice daily oral

Also known as: Ciclosporin, cyclosporin A, cyclosporin

Allo-HSCT + TLI + ATG

Mycophenolate mofetil (MMF) DRUG

15 mg/kg twice daily oral

Also known as: Cellcept

Allo-HSCT + TLI + ATG

Total lymphoid irradiation (TLI) RADIATION

80 cGy/fraction radiotherapy in 10 fractions.

Allo-HSCT + TLI + ATG

Methylprednisolone sodium succinate DRUG

1.0 mg/kg for 5 days by IV

Also known as: Solumedrol, Medrol, Depo-Medrol, P-Care D40, P-Care D80

Allo-HSCT + TLI + ATG

Best standard care 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

Also known as: Standard of Care (physician discretion), Regular medical care

Best Standard Care

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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.
• Fulminant liver failure
• Cirrhosis with evidence of portal hypertension or bridging fibrosis
• Alcoholic hepatitis
• Esophageal varices
• A history of bleeding esophageal varices
• Hepatic encephalopathy

Sponsors & Collaborators

• Stanford University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (5)

Kaiser Permanente Northern California

Hayward, California, 94545, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Univeristy of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute

Interventions

Hematopoietic Stem Cell Transplantation; Transplantation; Antilymphocyte Serum; thymoglobulin; Cyclosporine; Mycophenolic Acid; Methylprednisolone Hemisuccinate; Methylprednisolone; Methylprednisolone Acetate; Standard of Care

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Robert Lowsky, Professor of Medicine (Blood and Marrow Transplantation)
• Organization: Stanford University

rlowsky@stanford.edu

650-725-8950

Study Officials

• Robert Lowsky

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

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

Study Record Dates

• First Submitted: December 4, 2007
• First Posted: December 6, 2007
• Study Start: August 1, 2007
• Primary Completion: December 31, 2015
• Study Completion: December 31, 2015
• Last Updated: September 24, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)