Clinical trial NCT00568633: Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Leukemia, Myeloid
Leukemia
Acute Myeloid Leukemia (AML)
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2007-12-06
Enrollment: 58
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment assignment was based on availability of an HLA-matched donor.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Disease-free Survival (DFS)
timeFrame: 2 years
measure: Non-relapse Mortality
timeFrame: 2 years
measure: Relapse Rate
timeFrame: 2 years
measure: Transplant-related Mortality
timeFrame: 100 days and 6 months
measure: Complete Donor Hematopoietic Cell Chimerism
timeFrame: 2 years
measure: Early Graft Loss
timeFrame: 2 years
measure: Patients Completing the Intended Therapy in Both Arms
timeFrame: 2 years
Other outcomes:
Locations:
city: Hayward
country: United States
facility: Kaiser Permanente Northern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: Univeristy of California Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
Study officials:
affiliation: Stanford University
name: Robert Lowsky
role: PRINCIPAL_INVESTIGATOR
References: