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

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ClinicalTrials.gov Identifier: NCT00568633
Recruitment Status : Terminated (Poor accrual)
First Posted : December 6, 2007
Results First Posted : September 11, 2019
Last Update Posted : September 24, 2019
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Robert Lowsky, Stanford University

Tracking Information
First Submitted Date  ICMJE December 4, 2007
First Posted Date  ICMJE December 6, 2007
Results First Submitted Date  ICMJE August 16, 2019
Results First Posted Date  ICMJE September 11, 2019
Last Update Posted Date September 24, 2019
Actual Study Start Date  ICMJE August 2007
Actual Primary Completion Date December 31, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
Overall Survival (OS) [ Time Frame: 2 years ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2007)
Overall survival defined as the date of documented CR until the dte of the latest follow-up or death by any cause
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Disease-free Survival (DFS) [ Time Frame: 2 years ]
    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).
  • Non-relapse Mortality [ Time Frame: 2 years ]
    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).
  • Relapse Rate [ Time Frame: 2 years ]
    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).
  • Transplant-related Mortality [ Time Frame: 100 days and 6 months ]
    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).
  • Complete Donor Hematopoietic Cell Chimerism [ Time Frame: 2 years ]
    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.
  • Early Graft Loss [ Time Frame: 2 years ]
    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.
  • Patients Completing the Intended Therapy in Both Arms [ Time Frame: 2 years ]
    The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2007)
  • To determine if NMA HCT leads to a superior disease free survival (DFS) compared to conventional therapy
  • To determine the relapse rates and non-relapse mortality in both arms of the study
  • To determine in the transplant recipients the 100 day and six month transplant related mortality
  • To determine in the transplant recipients the incidence of complete donor hematopoietic cell chimerism and of primary graft loss
  • To determine the percentage of patients completing the intended therapy in both arms
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Treatment assignment was based on availability of an HLA-matched donor.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia, Myeloid
  • Leukemia
  • Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • 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.
    Other Names:
    • Hematopoietic stem cell transplantation (HSCT)
    • Peripheral blood stem cell (PBSC) transplantation
  • Drug: Anti-thymocyte globulin (ATG)
    1.5 mg/kg for 5 days by IV
    Other Names:
    • Thymoglobulin
    • Anti-thymocyte globulin (rabbit) (ATG)
  • Drug: Cyclosporine (CSP)
    6.25 mg/kg twice daily oral
    Other Names:
    • Ciclosporin
    • cyclosporin A
    • cyclosporin
  • Drug: Mycophenolate mofetil (MMF)
    15 mg/kg twice daily oral
    Other Name: Cellcept
  • 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
    Other Names:
    • Solumedrol
    • Medrol
    • Depo-Medrol
    • P-Care D40
    • P-Care D80
  • 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
    Other Names:
    • Standard of Care (physician discretion)
    • Regular medical care
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Procedure: Allogeneic HSCT
    • Drug: Anti-thymocyte globulin (ATG)
    • Drug: Cyclosporine (CSP)
    • Drug: Mycophenolate mofetil (MMF)
    • Radiation: Total lymphoid irradiation (TLI)
    • Drug: Methylprednisolone sodium succinate
  • Active Comparator: 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
    Intervention: Drug: Best standard care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 16, 2019)
58
Original Enrollment  ICMJE
 (submitted: December 4, 2007)
150
Actual Study Completion Date  ICMJE December 31, 2015
Actual Primary Completion Date December 31, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00568633
Other Study ID Numbers  ICMJE IRB-05567
97843 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT190 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Robert Lowsky, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Genzyme, a Sanofi Company
Investigators  ICMJE
Principal Investigator: Robert Lowsky Stanford University
PRS Account Stanford University
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP