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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00568633
Recruitment Status : Terminated (Poor accrual)
First Posted : December 6, 2007
Last Update Posted : November 18, 2016
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Robert Lowsky, 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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid Leukemia Acute Myeloid Leukemia (AML) Procedure: Hematopoietic Cell Transplantation Drug: Anti-Thymocyte Globulin Drug: Cyclosporine Drug: Cellcept Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : August 2007
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Arm Intervention/treatment
Experimental: Hematopoietic Cell Transplantation Procedure: Hematopoietic Cell Transplantation
Standard of care
Other Names:
  • Hematopoietic stem cell transplantation
  • HSCT

Drug: Anti-Thymocyte Globulin
1.5 mg/kg x 5 days, iv
Other Name: ATG

Drug: Cyclosporine
6.25mg/kgBID, po
Other Names:
  • Ciclosporin
  • cyclosporin A
  • cyclosporin

Drug: Cellcept
15mg/kgBID, po
Other Name: Mycophenolate mofetil

Primary Outcome Measures :
  1. Overall survival defined as the date of documented complete remission (CR) until the dte of the latest follow-up or death by any cause [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. To determine if Nonmyeloablative Host Conditioning (NMA HCT) leads to a superior disease free survival (DFS) compared to conventional therapy [ Time Frame: 2 years ]
  2. To determine the relapse rates and non-relapse mortality in both arms of the study [ Time Frame: 2 years ]
  3. To determine in the transplant recipients the 100 day and six month transplant related mortality [ Time Frame: 6 months ]
  4. To determine in the transplant recipients the incidence of complete donor hematopoietic cell chimerism and of primary graft loss [ Time Frame: 2 years ]
  5. To determine the percentage of patients completing the intended therapy in both arms [ Time Frame: 2 years ]

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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Both genders and individuals from all ethnic groups will be eligible.

  1. Patients greater than or equal to 50 years of age and less than or equal to 75 years of age.
  2. Patients with de novo AML based on FAB and WHO criteria.
  3. Patients with intermediate or unfavorable cytogenetic abnormalities based on SWOG Cytogenetic Criteria.
  4. Patients achieving a 1st morphologic CR, or CRp (a complete remission but with low platelets) following one or two courses of induction therapy. (See definition of CR on page 6.) CR must be documented no more than 8 weeks prior to the date of enrollment.
  5. Patients fit for nonmyeloablative transplantation or best treatment.
  6. Patients able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

  1. Patients with AML with favorable cytogenetic features based on SWOG Cytogenetic Criteria.
  2. Patients not in a Complete Remission at time of enrollment.
  3. Patients with treatment-related or MDS-related AML.
  4. CR documented >8 weeks prior to date of enrollment.
  5. Patients with active CNS disease as identified by positive CSF cytospin at time of enrollment.
  6. Patients with prior or concurrent malignancies except localized non-melanoma skin malignancies or treated cervical carcinoma in situ. Cancer treated with curative intent <5 years previously will not be allowed. Cancer treated with curative intent >5 years previously will be allowed. Patients with low grade lymphomas are eligible as long as they have not and do not require active treatment for control of their disease.
  7. Patients planned for allogeneic transplant using a full-dose conditioning, irrespective of knowledge of donor status.
  8. Patients whose life expectancy is severely limited (<1 year) by diseases other than malignancy.
  9. Karnofsky Performance Score <60.
  10. Patients who are pregnant or breastfeeding.
  11. Patients who are HIV seropositive.
  12. Patients who have an uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month.
  13. Patients with symptomatic coronary artery disease, uncontrolled congestive heart failure. Left Ventricular Ejection Fraction is not required to be measured, however if it is measured, patient is excluded if ejection fraction is <30%.
  14. Patients requiring supplementary continuous oxygen. DLCO is not required to be measured, however if it is measured, patient is excluded if DLCO <35%.
  15. Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension. Patients with any of the following liver function abnormalities will be excluded:

    1. Fulminant liver failure.
    2. Cirrhosis with evidence of portal hypertension or bridging fibrosis.
    3. Alcoholic hepatitis.
    4. Esophageal varices.
    5. A history of bleeding esophageal varices.
    6. Hepatic encephalopathy.
    7. Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time.
    8. Ascites related to portal hypertension.
    9. Chronic viral hepatitis with total serum bilirubin >3 mg/dL.
    10. Symptomatic biliary disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00568633

United States, California
Kaiser Permanente Northern California
Hayard, California, United States, 94545
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Univeristy of California Davis Medical Center
Sacramento, California, United States, 95817
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, West Virginia
West Virginia University Hospital
Morgantown, West Virginia, United States, 26506
Sponsors and Collaborators
Stanford University
Genzyme, a Sanofi Company
Principal Investigator: Louis Fehrenbacher Southern California Kaiser Permanente Group

Responsible Party: Robert Lowsky, Professor of Medicine, Stanford University Identifier: NCT00568633     History of Changes
Other Study ID Numbers: BMT190
97843 ( Other Identifier: Stanford University Alternate IRB Approval Number )
5567 ( Other Identifier: Stanford IRB )
First Posted: December 6, 2007    Key Record Dates
Last Update Posted: November 18, 2016
Last Verified: November 2013

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Mycophenolic Acid
Antilymphocyte Serum
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents