Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

NCT ID: NCT00630565

Last Updated: 2024-01-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-26
• Study Completion Date: 2022-07-28

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.

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.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed

cyclophosphamide

Intervention Type: DRUG

4 gm/m\^2 x 1 (day 0) and 60 mg/kg intravenous (IV) over 2 hours on days -3 and -2.

dexamethasone

Intervention Type: DRUG

20 mg/m\^2 x 4 doses every 12 hours given intravenously (IV) push before cytoxan on day 0 and then every 12 hours

etoposide

Intervention Type: DRUG

300 mg/m\^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)

bone marrow transplantation

Intervention Type: PROCEDURE

Day 0 infusion of bone marrow cells

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Day 0 infusion of peripheral blood stem cells

total-body irradiation

Intervention Type: RADIATION

165 cGy/dose given twice a day on days -7 through -4.

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).

Group Type: EXPERIMENTAL

sargramostim

Intervention Type: BIOLOGICAL

Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed

busulfan

Intervention Type: DRUG

4 mg/kg po in 4 divided doses (.8 mg/kg/dose orally every 6 hours) on days -7 through -4.

cyclophosphamide

Intervention Type: DRUG

4 gm/m\^2 x 1 (day 0) and 60 mg/kg intravenous (IV) over 2 hours on days -3 and -2.

dexamethasone

Intervention Type: DRUG

20 mg/m\^2 x 4 doses every 12 hours given intravenously (IV) push before cytoxan on day 0 and then every 12 hours

etoposide

Intervention Type: DRUG

300 mg/m\^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)

hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Stem cell infusion (\>48 hours after the last dose of cyclophosphamide)

Interventions

sargramostim

Given subcutaneously (SC) 10 μg/kg/day from day +3 until apheresis is completed

Intervention Type: BIOLOGICAL

busulfan

4 mg/kg po in 4 divided doses (.8 mg/kg/dose orally every 6 hours) on days -7 through -4.

Intervention Type: DRUG

cyclophosphamide

4 gm/m\^2 x 1 (day 0) and 60 mg/kg intravenous (IV) over 2 hours on days -3 and -2.

Intervention Type: 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

Intervention Type: DRUG

etoposide

300 mg/m\^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)

Intervention Type: DRUG

bone marrow transplantation

Day 0 infusion of bone marrow cells

Intervention Type: PROCEDURE

hematopoietic stem cell transplantation

Stem cell infusion (\>48 hours after the last dose of cyclophosphamide)

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Day 0 infusion of peripheral blood stem cells

Intervention Type: PROCEDURE

total-body irradiation

165 cGy/dose given twice a day on days -7 through -4.

Intervention Type: RADIATION

Other Intervention Names

G-CSF; Busulfex; Cytoxan; Decadron; VP-16; ABMT; HSCT; PBSCT; TBI

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
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel J. Weisdorf, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

0607M89052

Identifier Type: OTHER

Identifier Source: secondary_id

MT2006-13

Identifier Type: -

Identifier Source: org_study_id