Ex Vivo Expansion of Mafosfamide Purged CD34+ Cells in Patients With Acute Leukemia
| Status: | Terminated |
|---|---|
| Conditions: | Blood Cancer, Leukemia |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 70 |
| Updated: | 8/25/2018 |
| Start Date: | October 2005 |
| End Date: | January 2012 |
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.
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.
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.
- 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.
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.
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins The name Johns Hopkins has become synonymous...
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