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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.
 
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

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: Allogeneic HSCT Drug: Anti-thymocyte globulin (ATG) Drug: Cyclosporine (CSP) Drug: Mycophenolate mofetil (MMF) Radiation: Total lymphoid irradiation (TLI) Drug: Methylprednisolone sodium succinate Drug: Best standard care Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
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
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
Actual Study Start Date : August 2007
Actual Primary Completion Date : December 31, 2015
Actual Study Completion Date : December 31, 2015


Arm Intervention/treatment
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
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

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
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




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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.

  6. 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.

  7. 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



Information from the National Library of Medicine

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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
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

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 ClinicalTrials.gov identifier (NCT number): NCT00568633


Locations
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United States, California
Kaiser Permanente Northern California
Hayward, 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
Investigators
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Principal Investigator: Robert Lowsky Stanford University
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Responsible Party: Robert Lowsky, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00568633    
Other Study ID Numbers: IRB-05567
97843 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT190 ( Other Identifier: OnCore )
First Posted: December 6, 2007    Key Record Dates
Results First Posted: September 11, 2019
Last Update Posted: September 24, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cyclosporine
Mycophenolic Acid
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Cyclosporins
Thymoglobulin
Antilymphocyte Serum
Prednisolone hemisuccinate
Prednisolone phosphate
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