Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

Autologous Peripheral Blood Stem Cell Transplant for Acute Non-Lymphocytic Leukemia (ANLL)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00630565
• Other study ID #: MT2006-13
• Secondary ID: 0607M89052
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: July 26, 2006
• Est. completion date: July 28, 2022

Study information

• Verified date: January 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: July 28, 2022
• Est. primary completion date: July 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia

Intervention

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

Drug:
• busulfan
4 mg/kg po in 4 divided doses (.8 mg/kg/dose orally every 6 hours) on days -7 through -4.
• cyclophosphamide
4 gm/m^2 x 1 (day 0) and 60 mg/kg intravenous (IV) over 2 hours on days -3 and -2.
• 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
• etoposide
300 mg/m^2/day x 2 days (day 0-1) over 3 hours intravenously (IV)

Procedure:
• bone marrow transplantation
Day 0 infusion of bone marrow cells
• hematopoietic stem cell transplantation
Stem cell infusion (>48 hours after the last dose of cyclophosphamide)
• peripheral blood stem cell transplantation
Day 0 infusion of peripheral blood stem cells

Radiation:
• total-body irradiation
165 cGy/dose given twice a day on days -7 through -4.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Engraftment	Percentage of Participants with Engraftment measured by myeloid, platelet, and erythroid recovery	30 Days Post Transplant
Secondary	Percentage of Participants With Disease Response	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
Secondary	Treatment Failure	Percentage of participants experiencing treatment failure.	2 years Post Transplant
Secondary	Percent of Patients With Various Late Effects	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
Secondary	Disease-free Survival	Disease-free survival 2 years Post Transplant	2 years Post Transplant
Secondary	Percentage of Patients With Adequate Cells Collected	The proportion of primed patients with adequate number of cells collected will be calculated.	Pre-Transplant