Clinical Trials /

Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

NCT00630565

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia
  • Official Title: Autologous Peripheral Blood Stem Cell Transplant for Acute Non-Lymphocytic Leukemia (ANLL)

Clinical Trial IDs

  • ORG STUDY ID: MT2006-13
  • SECONDARY ID: 0607M89052
  • NCT ID: NCT00630565

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
sargramostimG-CSFBone Marrow Transplant (2-70 Years old)
busulfanBusulfexBone Marrow Transplant (less and 2 years old)
cyclophosphamideCytoxanBone Marrow Transplant (2-70 Years old)
dexamethasoneDecadronBone Marrow Transplant (2-70 Years old)
etoposideVP-16Bone Marrow Transplant (2-70 Years old)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Bone Marrow Transplant (2-70 Years old)ExperimentalPatients 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).
  • cyclophosphamide
  • dexamethasone
  • etoposide
Bone Marrow Transplant (less and 2 years old)ExperimentalPatients 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).
  • busulfan
  • cyclophosphamide
  • dexamethasone
  • etoposide

Eligibility Criteria

        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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Engraftment
Time Frame:30 Days Post Transplant
Safety Issue:
Description:Median Days from bone marrow transplant engraftment to cell recovery. Rate of myeloid, platelet, and erythroid recovery

Secondary Outcome Measures

Measure:Disease Response
Time Frame:2 years Post Transplant
Safety Issue:
Description:Disease evaluation will be completed approximately 100 days after stem cell infusion and every 6 months, 1year, and until 2 years after infusion.
Measure:Time to Treatment Failure
Time Frame:2 years Post Transplant
Safety Issue:
Description:
Measure:Percent of patients with various late effects
Time Frame:2 years Post Transplant
Safety Issue:
Description:Description: (e.g., thyroid function abnormalities - T4, TSH, gonadal abnormalities, cataracts, pulmonary dysfunctions, growth and development abnormalities, and second malignant neoplasms)
Measure:Disease-free survival
Time Frame:2 years Post Transplant
Safety Issue:
Description:Description: Rate of relapse by Kaplan-Meier estimate.
Measure:Number of Patients with Adequate Cells Collected
Time Frame:Pre-Transplant
Safety Issue:
Description: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.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • adult acute myeloid leukemia in remission
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • childhood acute myeloid leukemia in remission

Last Updated