Know Cancer

or
forgot password

Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells


Phase 2
N/A
N/A
Not Enrolling
Both
Leukemia

Thank you

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 CenterBaltimore, Maryland  21201