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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / 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).
Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed
Other Names:
  • G-CSF
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
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
300 mg/m^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)
Other Names:
  • VP-16
Day 0 infusion of bone marrow cells
Other Names:
  • ABMT
Day 0 infusion of peripheral blood stem cells
Other Names:
  • PBSCT
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).
Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed
Other Names:
  • G-CSF
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
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
300 mg/m^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)
Other Names:
  • VP-16
4 mg/kg po in 4 divided doses (.8 mg/kg/dose orally every 6 hours) on days -7 through -4.
Other Names:
  • Busulfex
Stem cell infusion (>48 hours after the last dose of cyclophosphamide)
Other Names:
  • HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Engraftment
Time Frame: 30 Days Post Transplant
Percentage of Participants with Engraftment measured by myeloid, platelet, and erythroid recovery
30 Days Post Transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Disease Response
Time Frame: 2 years Post Transplant
Disease evaluation will be completed approximately 100 days after stem cell infusion and every 6 months, 1 year, and until 2 years after infusion.
2 years Post Transplant
Treatment Failure
Time Frame: 2 years Post Transplant
Percentage of participants experiencing treatment failure.
2 years Post Transplant
Percent of Patients With Various Late Effects
Time Frame: 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)
2 years Post Transplant
Disease-free Survival
Time Frame: 2 years Post Transplant
Disease-free survival 2 years Post Transplant
2 years Post Transplant
Percentage of Patients With Adequate Cells Collected
Time Frame: Pre-Transplant
The proportion of primed patients with adequate number of cells collected will be calculated.
Pre-Transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2006

Primary Completion (Actual)

July 28, 2022

Study Completion (Actual)

July 28, 2022

Study Registration Dates

First Submitted

March 6, 2008

First Submitted That Met QC Criteria

March 6, 2008

First Posted (Estimated)

March 7, 2008

Study Record Updates

Last Update Posted (Estimated)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 9, 2024

Last Verified

January 1, 2024

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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