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
  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.


Condition Intervention Phase
Leukemia
Biological: sargramostim
Drug: busulfan
Drug: cyclophosphamide
Drug: dexamethasone
Drug: etoposide
Procedure: bone marrow transplantation
Procedure: hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous Peripheral Blood Stem Cell Transplant for Acute Non-Lymphocytic Leukemia (ANLL)

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 60
Study Start Date: July 2006
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 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: 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 (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 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: hematopoietic stem cell transplantation
Stem cell infusion (>48 hours after the last dose of cyclophosphamide)
Other Name: HSCT

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.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00630565

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Timothy Krepski    612-273-2800    tkrepsk1@fairview.org   
Principal Investigator: Daniel J. Weisdorf, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Daniel J. Weisdorf, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00630565     History of Changes
Other Study ID Numbers: MT2006-13, 0607M89052
Study First Received: March 6, 2008
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Cyclophosphamide
Etoposide phosphate
Dexamethasone
Etoposide
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 01, 2014