Ex Vivo Expansion of Mafosfamide Purged CD34+ Cells in Patients With Acute Leukemia

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Terminated

CT.gov ID

NCT00245115

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected. Treating stem cells collected from the patient's blood or bone marrow with chemotherapy in the laboratory removes any remaining cancer cells. Chemotherapy or radiation therapy is given to the patient to prepare the bone marrow for stem cell transplant. The treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This clinical trial is studying how well an autologous peripheral stem cell or bone marrow transplant using laboratory-treated cells works in treating patients with acute leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: filgrastim Drug: busulfan Drug: cyclophosphamide Procedure: in vitro-treated bone marrow transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation	Phase 1

Detailed Description

OBJECTIVES:

Determine the feasibility of ex vivo expanded mafosfamide-purged CD34-positive cells for autologous peripheral blood stem cell or bone marrow transplantation in patients with acute leukemia.
Determine the duration of aplasia associated with the use of ex vivo cytokine expanded mafosfamide-purged cells in patients treated with this regimen.
Determine, preliminarily, the event-free survival of patients treated with this regimen.

OUTLINE: This is a pilot study.

Mobilization and stem cell collection: Patients receive cyclophosphamide IV and filgrastim (G-CSF) subcutaneously (SC) or IV once daily for 7-14 days followed by leukapheresis to collect peripheral blood stem cells (PBSCs). Some patients may also undergo bone marrow (BM) harvest if sufficient PBSCs are not collected. Patients with a sufficient number of stem cells or BM (5 x 10^{6 PBSC/kg or 3 x 10}8 BM cells/kg) proceed to autologous PBSC transplantation (PBSCT) or BM transplantation (BMT).
CD34-positive cell selection and mafosfamide purging: Collected PBSCs and/or BM are treated in the laboratory to isolate CD34-positive cells. A minimum of 1 x 10^{6
nucleated CD34-positive BM cells/kg or 2 x 10}6 nucleated CD34-positive PBSCs/kg must be available after selection to proceed to mafosfamide-purging. The selected cells are then treated in vitro with mafosfamide to purge remaining leukemic cells. One third of the mafosfamide-purged cells are then cryopreserved for future use and 2/3 of the mafosfamide-purged cells proceed to ex vivo expansion.
Ex vivo expansion: The remaining CD34-positive mafosfamide-purged cells are treated in vitro with stem cell factor, G-CSF, and recombinant human thrombopoietin and incubated for 12-14 days.
Myeloablative therapy: Patients receive busulfan on days -9 to -6 and cyclophosphamide on days -5 to -2.
PBSCT or BMT: Patients undergo autologous PBSCT or BMT using CD34-positive mafosfamide-purged cryopreserved cells and ex vivo expanded CD34-positive mafosfamide-purged cells on day 0 followed by G-CSF SC or IV once daily until blood counts recover.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Ex Vivo Expansion of Mafosfamide Purged CD34+ Cells in Patients With Acute Leukemia

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Jan 1, 2012

Outcome Measures

Primary Outcome Measures

Number of patients infused with Mf-treated cells with successful expansion [2 weeks]
Number of patients with successful expansion of a CD34 selected, mafosfamide purged autograft.

Secondary Outcome Measures

Duration of aplasia as determined by Number of Days to Absolute Neutrophil Count (ANC) recovery [1 month]
Event free survival [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of acute leukemia meeting 1 of the following criteria:
High-risk acute myeloid leukemia (AML) in first complete remission (CR) with no matched family donor available, including any of the following types:
Secondary AML
AML with chromosome 5 or 7 abnormalities
AML with trisomy 8
AML with 6;9 chromosomal translocation
AML with 11q23 chromosomal abnormality
AML with multiple or complex chromosomal abnormalities
AML with FAB M6 or M7
AML in second CR (CR2) with no eligible HLA-identical sibling donor available
High-risk acute lymphoblastic leukemia (ALL) with no eligible HLA-identical sibling donor available, including any of the following types:
Philadelphia chromosome-positive ALL
ALL with 11q23 chromosomal abnormality
ALL in CR2
Eligible for and willing to undergo bone marrow transplantation
No intermediate- or good-risk acute leukemia in CR1

Exclusion Criteria

Availability of a suitable matched HLA-identical sibling marrow donor
Intermediate or good risk acute leukemia in CR1 (39)
Age greater than 70
Weight less than 10 kg
Any risk of pregnancy - all female patients must have an effective form of contraception or be infertile due to hysterectomy, fallopian tube, surgery or premature menopause.
HIV Infection: Patients must be HIV negative for inclusion.
Poor organ function as defined in the BMT Policies and Procedures Manual.