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

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ClinicalTrials.gov Identifier: NCT00003727
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : November 4, 2019
Sponsor:
Collaborator:
University of Maryland Greenebaum Cancer Center
Information provided by:
University of Maryland, Baltimore

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date November 4, 2019
Study Start Date  ICMJE March 1999
Actual Primary Completion Date March 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2007)
  • Response (i.e., major cytogenetic or molecular response) within 12 months after completion of study therapy
  • Mortality rate
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00003727 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy and Peripheral Stem Cell Transplantation Followed by Immunotherapy in Treating Patients With Chronic Myelogenous Leukemia
Official Title  ICMJE Autotransplantation for Chronic Myelogenous Leukemia (CML) Followed by Immunotherapy With Ex-Vivo Expanded Autologous T Cells
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with a peripheral stem cell transplant 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: This phase II trial is studying giving chemotherapy together with a peripheral stem cell transplant followed by immunotherapy to see how well it works in treating patients with chronic phase chronic myelogenous leukemia.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Biological: filgrastim
  • Biological: recombinant interferon alfa
  • Biological: sargramostim
  • Biological: therapeutic autologous lymphocytes
  • Drug: carmustine
  • Drug: cyclophosphamide
  • Drug: etoposide
  • Drug: gemcitabine hydrochloride
  • Drug: melphalan
  • Procedure: bone marrow ablation with stem cell support
  • Procedure: in vitro-treated peripheral blood stem cell transplantation
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: April 9, 2007)
22
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 2008
Actual Primary Completion Date March 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 120 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00003727
Other Study ID Numbers  ICMJE CDR0000066839
MSGCC-9851
MSGCC-1198006
NCI-V98-1513
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party UM Greenebaum Cancer Center
Study Sponsor  ICMJE University of Maryland, Baltimore
Collaborators  ICMJE University of Maryland Greenebaum Cancer Center
Investigators  ICMJE
Study Chair: Aaron P. Rapoport, MD University of Maryland Greenebaum Cancer Center
PRS Account University of Maryland, Baltimore
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP