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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00568633
• Other study ID #: IRB-05567
• Secondary ID: 97843BMT190
• Status: Terminated
• Phase: Phase 3
• Start date: August 2007
• Est. completion date: December 31, 2015

Study information

• Verified date: August 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 58
• Est. completion date: December 31, 2015
• Est. primary completion date: December 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Procedure:
• 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.

Drug:
• 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

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

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

Locations

Country	Name	City	State
United States	Kaiser Permanente Northern California	Hayward	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Univeristy of California Davis Medical Center	Sacramento	California
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease-free Survival (DFS)	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).	2 years
Secondary	Non-relapse Mortality	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).	2 years
Secondary	Relapse Rate	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).	2 years
Secondary	Transplant-related Mortality	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).	100 days and 6 months
Secondary	Complete Donor Hematopoietic Cell Chimerism	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.	2 years
Secondary	Early Graft Loss	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.	2 years
Secondary	Patients Completing the Intended Therapy in Both Arms	The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion	2 years