Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells
N/A
N/A
Both
Leukemia
Trial Information
Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells
OBJECTIVES:
- Determine the feasibility of ex vivo expansion and reinfusion of autologous CD4+ T
cells after interferon therapy or high-dose chemotherapy with CD34-selected autologous
peripheral blood stem cell rescue in patients with chronic phase chronic myelogenous
leukemia (CML).
- Determine the frequency of hematologic, cytogenetic, and molecular remissions of CML
following infusion of ex vivo expanded T cells.
OUTLINE: Patients undergo mononuclear cell leukapheresis to obtain T cells for ex-vivo
expansion, preferably before they receive interferon alfa subcutaneously (SC) daily on a
therapeutic trial.
At least 1 month after interferon is stopped, mobilization chemotherapy is administered.
Patients receive cyclophosphamide IV over 12 hours on day 0, etoposide IV over 2 hours on
day 1, sargramostim (GM-CSF) SC on days 3 and 4, and filgrastim (G-CSF) SC beginning on day
5. Peripheral blood stem cells (PBSC) are collected by leukapheresis when blood cell counts
have recovered.
Approximately 2-3 weeks later, high-dose chemotherapy begins. Patients receive gemcitabine
IV over 100 minutes on day -5, carmustine IV over 2 hours on day -2, followed 6 hours later
by gemcitabine IV again, and melphalan IV over 20 minutes on day -1. CD34 selected PBSCs are
infused on day 0, at least 18 hours after melphalan administration. Patients receive GM-CSF
SC beginning on day 1 and continuing until blood cell counts recover.
Patients then receive ex vivo expanded autologous T cells on day 14 after
autotransplantation. Interferon alfa is administered three times a week starting about 3
months after transplantation.
Patients who only receive expanded T cells, without high-dose chemotherapy and
autotransplantation, but show no response after 3 months, may proceed to autotransplantation
followed by a second ex vivo expanded T-cell infusion.
Patients are followed at 1, 2, 3, 6, 9, and 12 months, then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 7-22 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of chronic myelogenous leukemia based on clinical features and molecular
evidence for bcr/abl gene rearrangement
- First or second chronic phase at the time of stem cell collection
- Ineligible for allogeneic transplantation
- Should receive interferon alfa (IFN-A) with or without low-dose cytarabine for at
least 3-6 months before autotransplantation and meet one of the following conditions:
- After 3 months of IFN-A, hematologic response is partial or less and poor
clinical feature was present at diagnosis
- After 6 months of IFN-A, hematologic response is partial or complete (but 100%
Ph+) and poor clinical feature was present at diagnosis
- After 9 or 12 months of IFN-A, no cytogenetic response occurred (100% Ph+),
regardless of pretreatment clinical features
- After at least 12 months of IFN-A (or on 2 separate tests, 3 months apart), only
minor cytogenetic response (35-90% Ph+) occurred, then eligible for ex vivo
expanded autologous T cells only (without high-dose chemotherapy or
autografting) or high-dose therapy plus autographing at physicians' discretion
- After at least 12 months of IFN-A (or on 2 tests, 3 months apart), major but not
complete cytogenetic response (0-34% Ph+) occurred, then eligible for ex vivo
expanded autologous T cells only (without high-dose chemotherapy or
autografting)
- After at least 18 months of IFN-A, complete cytogenetic response (0% Ph+)
occurred but remain positive for BCR/ABL gene rearrangement then eligible for ex
vivo expanded autologous T cells only (without high-dose chemotherapy or
autografting)
- Unsatisfactory response to prior STI571 allowed (regardless of prior IFN-A)
PATIENT CHARACTERISTICS:
Age:
- Not specified
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin no greater than 2 times upper limit of normal (ULN) (unless due to
Gilbert's disease)
- AST and ALT no greater than 2 times ULN (unless liver involvement with CML)
Renal:
- Creatinine no greater than 2.5 mg/dL
Cardiovascular:
- LVEF at least 45% (lower allowed if no significant functional impairment)
Pulmonary:
- FEV_1, FVC, and DLCO at least 50% predicted
Other:
- No active infections requiring IV antibiotics
- HIV negative
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- At least 1 month since prior interferon
Chemotherapy:
- At least 1 week since hydroxyurea before leukapheresis
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response (i.e., major cytogenetic or molecular response) within 12 months after completion of study therapy
Safety Issue:
No
Principal Investigator
Aaron P. Rapoport, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Maryland Greenebaum Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000066839
NCT ID:
NCT00003727
Start Date:
March 1999
Completion Date:
February 2008
Related Keywords:
- Leukemia
- relapsing chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- Philadelphia chromosome positive chronic myelogenous leukemia
- Philadelphia chromosome negative chronic myelogenous leukemia
- childhood chronic myelogenous leukemia
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Name | Location |
|---|---|
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
