Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00630565
First received: March 6, 2008
Last updated: March 4, 2014
Last verified: March 2014

March 6, 2008
March 4, 2014
July 2006
December 2015   (final data collection date for primary outcome measure)
Engraftment [ Time Frame: Days ] [ Designated as safety issue: No ]
Median Days from bone marrow transplant engraftment to cell recovery. Rate of myeloid, platelet, and erythroid recovery
  • Percent of patients with various late effects (e.g., thyroid function abnormalities, gonadal abnormalities, cataracts, pulmonary dysfunctions, growth and development abnormalities, and second malignant neoplasms) [ Designated as safety issue: Yes ]
  • Rate of myeloid, platelet, and erythroid recovery [ Designated as safety issue: No ]
  • Disease-free survival rate [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00630565 on ClinicalTrials.gov Archive Site
  • Disease Response [ Time Frame: Day 100, 6 months, 1 year, 2 years ] [ Designated as safety issue: No ]
    Disease evaluation will be completed approximately 100 days after stem cell infusion and every 6 months, 1year, and until 2 years after infusion.
  • Time to Treatment Failure [ Time Frame: from date of stem cell infusion to date of recurrence. ] [ Designated as safety issue: No ]
  • Percent of patients with various late effects [ Time Frame: Years 1, 2, 3, 4 and 5 ] [ Designated as safety issue: Yes ]
    Description: (e.g., thyroid function abnormalities - T4, TSH, gonadal abnormalities, cataracts, pulmonary dysfunctions, growth and development abnormalities, and second malignant neoplasms)
  • Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Description: Rate of relapse by Kaplan-Meier estimate.
  • Number of Patients with Adequate Cells Collected [ Time Frame: Pre-Transplant ] [ Designated as safety issue: No ]
    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.
Not Provided
Not Provided
Not Provided
 
Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia
Autologous Peripheral Blood Stem Cell Transplant for Acute Non-Lymphocytic Leukemia (ANLL)

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Biological: sargramostim
    Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed
    Other Name: 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 Name: 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 Name: 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 Name: Decadron
  • Drug: etoposide
    300 mg/m^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)
    Other Name: VP-16
  • Procedure: bone marrow transplantation
    Day 0 infusion of bone marrow cells
    Other Name: ABMT
  • Procedure: hematopoietic stem cell transplantation
    Stem cell infusion (>48 hours after the last dose of cyclophosphamide)
    Other Name: HSCT
  • Procedure: peripheral blood stem cell transplantation
    Day 0 infusion of peripheral blood stem cells
    Other Name: PBSCT
  • Radiation: total-body irradiation
    165 cGy/dose given twice a day on days -7 through -4.
    Other Name: TBI
  • 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).
    Interventions:
    • Biological: sargramostim
    • Drug: cyclophosphamide
    • Drug: dexamethasone
    • Drug: etoposide
    • Procedure: bone marrow transplantation
    • Procedure: peripheral blood stem cell transplantation
    • Radiation: total-body irradiation
  • 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).
    Interventions:
    • Biological: sargramostim
    • Drug: busulfan
    • Drug: cyclophosphamide
    • Drug: dexamethasone
    • Drug: etoposide
    • Procedure: hematopoietic stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
December 2015
December 2015   (final data collection date for primary outcome measure)

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.
Both
up to 70 Years
No
United States
 
NCT00630565
MT2006-13, 0607M89052
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Daniel J. Weisdorf, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
March 2014

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