Clinical Trial: Chemotherapy and Peripheral Stem Cell Transplantation Followed by Immunotherapy in Treating Patients With Chronic Myelogenous Leukemia

This study is currently recruiting patients.

Sponsored by: University of Maryland Greenebaum Cancer Center
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation and immunotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy and peripheral stem cell transplantation followed by immunotherapy in treating patients who have chronic phase chronic myelogenous leukemia.

Condition Treatment or Intervention Phase
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
 Drug: autologous lymphocytes
 Drug: carmustine
 Drug: cyclophosphamide
 Drug: etoposide
 Drug: filgrastim
 Drug: gemcitabine
 Drug: interferon alfa
 Drug: melphalan
 Drug: sargramostim
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: chemotherapy
 Procedure: colony-stimulating factor therapy
 Procedure: cytokine therapy
 Procedure: high-dose chemotherapy
 Procedure: in vitro-treated peripheral blood stem cell transplantation
 Procedure: interferon therapy
 Procedure: leukocyte therapy
 Procedure: peripheral blood lymphocyte therapy
Phase II

MedlinePlus related topics:  Bone Marrow Diseases;   Immune System and Disorders;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood;   Lymphatic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Phase II Study of High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation Followed by Immunotherapy with Autologous T Cells in Patients With Chronic Phase Chronic Myelogenous Leukemia

Further Study Details: 

OBJECTIVES:

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.

Eligibility

Genders Eligible for Study:  Both

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

Location and Contact Information


Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Aaron P. Rapoport, MD  410-328-1230    arapoport@umm.edu 

Study chairs or principal investigators

Aaron P. Rapoport, MD,  Study Chair,  University of Maryland Greenebaum Cancer Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000066839; MSGCC-9851; MSGCC-1198006; NCI-V98-1513; NCT00003727
Record last reviewed:  September 2003
Last Updated:  December 6, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003727
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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