Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Recruiting
CT.gov ID
NCT00630565
Collaborator
(none)
60
Enrollment
1
Location
2
Arms
196.2
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy and colony-stimulating factors, such as G-CSF, may increase the number of stem cells in the blood. The stem cells are collected from the patient's blood and stored. Chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This clinical trial is studying how well an autologous stem cell transplant works in treating patients with acute myeloid leukemia.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2/Phase 3

Detailed Description

OBJECTIVES:
  • To assess whether sufficient peripheral blood stem cells (PBSC) can be collected from patients with acute myeloid leukemia (AML) using cyclophosphamide, etoposide, and granulocyte-colony stimulating factor (G-CSF) mobilization.

  • To assess the rate of myeloid, platelet, and erythroid recovery following autologous PBSC transplant.

  • To assess the disease-free survival rate of patients with AML receiving PBSC auto grafts.

OUTLINE:
  • Chemotherapy and filgrastim (G-CSF) priming for PBSC collection: Patients receive cyclophosphamide IV on day 0; etoposide IV over 3 hours on days 0 and 1; and oral dexamethasone twice daily on days 0 and 1. Patients also receive G-CSF subcutaneously (SC) beginning on day 3 and continuing until apheresis is complete. After blood counts recover, apheresis is performed in 4-6 daily planned collections until the minimum CD34+ cell dose of > 2.5 x 10^6 cells/kg is achieved. If the minimum CD34+ cell dose is not achieved after 6 apheresis collections, patients undergo bone marrow examination including a bone marrow biopsy and aspiration, at the termination of the PBSC collection to confirm remission. If remission is confirmed, and if peripheral counts and marrow cellularity are sufficient, the patient remains off G-CSF for 7 days and receives sargramostim (GM-CSF) for 5 days to increase the marrow cellularity, after which a bone marrow harvest is performed.

  • Bone marrow harvest without prior PBSC collection: Children will undergo primed bone marrow harvest comprising GM-CSF IV or SC for 5 days prior to harvest to increase cellularity and then marrow is harvested. Marrow and blood specimens are also obtained with the initial bone marrow evaluation and at the time of harvest if a cytogenetic abnormality was previously described. Other patients who are unable to undergo PBSC collection may proceed with a bone harvest at the discretion of the protocol chairperson.

  • Cytoreductive regimen:

  • Patients over 2 years old: Patients undergo total body irradiation (TBI) twice daily on days -7 to -4 (total of 8 fractions), cyclophosphamide IV over 2 hours on days -3 and -2, followed by a 1-day rest period on day -1.

  • Patients under 2 years old and patients who cannot undergo TBI: Patients receive busulfan IV or orally every 6 hours on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, followed by a 1-day rest period on day -1.

  • Stem cell transplantation: All patients undergo autologous PBSC and/or bone marrow infusion on day 0. Patients also receive G-CSF IV or SC beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 5 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Autologous Peripheral Blood Stem Cell Transplant for Acute Non-Lymphocytic Leukemia (ANLL)
Actual Study Start Date :
Jul 26, 2006
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Bone Marrow Transplant (2-70 Years old)

Patients over the age of two will receive a cytoreductive regimen of total-body irradiation and cyclophosphamide (TBI/CY) as well as sargramostim, dexamethasone, etoposide, transplantation (bone marrow transplantation/hematopoietic stem cell transplantation/peripheral blood stem cell transplantation).

Biological: sargramostim
Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed
Other Names:
  • G-CSF
  • Drug: cyclophosphamide
    4 gm/m^2 x 1 (day 0) and 60 mg/kg intravenous (IV) over 2 hours on days -3 and -2.
    Other Names:
  • Cytoxan
  • Drug: dexamethasone
    20 mg/m^2 x 4 doses every 12 hours given intravenously (IV) push before cytoxan on day 0 and then every 12 hours
    Other Names:
  • Decadron
  • Drug: etoposide
    300 mg/m^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)
    Other Names:
  • VP-16
  • Procedure: bone marrow transplantation
    Day 0 infusion of bone marrow cells
    Other Names:
  • ABMT
  • Procedure: peripheral blood stem cell transplantation
    Day 0 infusion of peripheral blood stem cells
    Other Names:
  • PBSCT
  • Radiation: total-body irradiation
    165 cGy/dose given twice a day on days -7 through -4.
    Other Names:
  • TBI
  • Experimental: Bone Marrow Transplant (less and 2 years old)

    Patients under the age of two, and patients who cannot receive total body irradiation (TBI), will receive a cytoreductive regimen of Busulfan and cyclophosphamide (BU/CY) as per the Johns Hopkins University Hospital regimen as well as sargramostim, dexamethasone, etoposide, transplantation (bone marrow transplantation/hematopoietic stem cell transplantation/peripheral blood stem cell transplantation).

    Biological: sargramostim
    Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed
    Other Names:
  • G-CSF
  • Drug: busulfan
    4 mg/kg po in 4 divided doses (.8 mg/kg/dose orally every 6 hours) on days -7 through -4.
    Other Names:
  • Busulfex
  • Drug: cyclophosphamide
    4 gm/m^2 x 1 (day 0) and 60 mg/kg intravenous (IV) over 2 hours on days -3 and -2.
    Other Names:
  • Cytoxan
  • Drug: dexamethasone
    20 mg/m^2 x 4 doses every 12 hours given intravenously (IV) push before cytoxan on day 0 and then every 12 hours
    Other Names:
  • Decadron
  • Drug: etoposide
    300 mg/m^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)
    Other Names:
  • VP-16
  • Procedure: hematopoietic stem cell transplantation
    Stem cell infusion (>48 hours after the last dose of cyclophosphamide)
    Other Names:
  • HSCT
  • Outcome Measures

    Primary Outcome Measures

    1. Engraftment [30 Days Post Transplant]

      Median Days from bone marrow transplant engraftment to cell recovery. Rate of myeloid, platelet, and erythroid recovery

    Secondary Outcome Measures

    1. Disease Response [2 years Post Transplant]

      Disease evaluation will be completed approximately 100 days after stem cell infusion and every 6 months, 1year, and until 2 years after infusion.

    2. Time to Treatment Failure [2 years Post Transplant]

    3. Percent of patients with various late effects [2 years Post Transplant]

      Description: (e.g., thyroid function abnormalities - T4, TSH, gonadal abnormalities, cataracts, pulmonary dysfunctions, growth and development abnormalities, and second malignant neoplasms)

    4. Disease-free survival [2 years Post Transplant]

      Description: Rate of relapse by Kaplan-Meier estimate.

    5. Number of Patients with Adequate Cells Collected [Pre-Transplant]

      Description: Can sufficient PBMC be collected with the Cy/VP-16/G-CSF priming regimen? The proportion of primed patients with adequate number of cells collected will be calculated.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Children under the age of two are eligible for this protocol, but will not receive total body irradiation. Instead, children under the age of two will receive Busulfan/Cyclophosphamide (Bu/Cy) conditioning as the preparative regimen in order to obviate deleterious effects of radiation at this age. Patients who cannot receive total body irradiation (TBI) (for example those with prior radiation therapy) will also receive the Bu/CY conditioning.

    • Acute myeloid leukemia (AML)

    • All children and adults less than the age of 70 with AML who have achieved a first or second bone marrow remission are eligible for this protocol. Patients must undergo peripheral blood stem cell collection or marrow harvest while in remission and must not be expected to have better outcomes with allogeneic transplantation.

    • Patients with cytogenetic abnormalities suggesting an improved prognosis [t(8:21), t(15;17) and inv(16)] will be eligible for transplantation in first remission.

    • Allogeneic transplant with an HLA-identical sibling will be recommended for patients <55 years. If the patient refuses allogeneic transplant, they may still be eligible for this protocol.

    Exclusion Criteria:
    • Patients can also be deemed not eligible for transplant because of specific organ toxicity. Specifically, patients with pre-existing compromise to the heart, lungs, kidney, CNS or liver may be excluded:

    • Eastern Cooperative Oncology Group (ECOG) Performance status: 0 or 1

    • Heart - The patient must be free of symptoms of uncontrolled cardiac disease, and must not have compromised cardiac function detected by ECHO or by gated cardiac blood flow scan (MUGA) LVEF >45%).

    • Kidney - The patient must have a corrected creatinine clearance >50% of normal.

    • Liver - The total serum bilirubin < 2.5 mg/dL; ALT <2 x upper limit of normal.

    • Lung - Patients must have no significant obstructive airways disease or resting hypoxemia (PO2 <80), and must have acceptable diffusion capacity (DLCO > 50% of predicted).

    • Central Nervous System (CNS): Patients must be free of active or ongoing ischemic or degenerative CNS disease and no active or resistant CNS leukemia.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Masonic Cancer Center, University of MinnesotaMinneapolisMinnesotaUnited States55455

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

    • Principal Investigator: Daniel J. Weisdorf, MD, Masonic Cancer Center, University of Minnesota

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00630565
    Other Study ID Numbers:
    • MT2006-13
    • 0607M89052
    First Posted:
    Mar 7, 2008
    Last Update Posted:
    Jan 22, 2021
    Last Verified:
    Jan 1, 2021

    Study Results

    No Results Posted as of Jan 22, 2021