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Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia
This study has been completed.

First Received on February 14, 2002.   Last Updated on June 4, 2011   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00030394
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: This phase II trial is studying imatinib mesylate to see how well it works in treating patients with chronic myelogenous leukemia.


Condition Intervention Phase
Leukemia
Drug: imatinib mesylate
Phase II

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Gleevec in Ph+ Chronic Phase Chronic Myelogenous Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Pharmacokinetics [ Designated as safety issue: No ]
  • Toxic effects [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate of hematological, cytogenetic, and molecular responses at 3, 6, and 12 months [ Designated as safety issue: No ]

Estimated Enrollment: 109
Study Start Date: September 2002
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the response rate in patients with Philadelphia chromosome positive chronic phase chronic myelogenous leukemia treated with imatinib mesylate.
  • Determine the disease-free survival of patients treated with this drug.
  • Determine the pharmacokinetics of this drug in these patients.
  • Determine the toxic effects of this drug in these patients.
  • Determine the rates of hematological, cytogenetic, and molecular response and time to response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients are stratified according to disease (chronic myelogenous leukemia [CML] in first chronic phase after failing interferon therapy or demonstrating intolerance to interferon [closed to accrual as of 12/05/03] vs CML relapsing after stem cell transplantation or in second or subsequent chronic phase [closed to accrual as of 7/29/05] vs newly diagnosed CML in first chronic phase with no prior treatment [closed to accrual as of 7/29/05] vs newly diagnosed CML in first chronic phase with no prior treatment).

Patients receive oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who fail to achieve a complete hematologic response after 3 courses or a partial or complete cytogenic response after 6 courses are removed from the study.

PROJECTED ACCRUAL: A total of 109 patients (30 for stratum I [closed to accrual as of 12/05/03] and stratum II [closed to accrual as of 7/29/05], 34 for stratum III [closed to accrual as of 7/29/05], and 45 for stratum IV) will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of Philadelphia chromosome positive (Ph+) chronic phase chronic myelogenous leukemia (CML)
  • Stratum I (closed to accrual as of 12/05/03):

    • CML in first chronic phase with resistance to interferon alfa (IFN-A) therapy defined as one of the following:

      • WBC count at least 20,000/mm^3 after at least 3 months of treatment with an IFN-A-containing regimen
      • Rising WBC count (at least 100% increase to a level of at least 20,000/mm^3) by two samples at least two weeks apart while receiving treatment with an IFN-A-containing regimen
      • At least 66% Ph+ cells in bone marrow after 1 year of IFN-A therapy
      • At least 30% increase in Ph+ cells in bone marrow after IFN-A-induced cytogenetic response while continuing to receive IFN-A therapy OR
    • Intolerance to interferon therapy defined as more than two grade 2 toxic effects or any grade 3 toxic effect related to interferon therapy, except grade 3 fever, that is persistent beyond the first 28-day course of therapy and unresponsive to standard supportive care interventions
  • Stratum II (closed to accrual as of 7/29/05): CML recurring after stem cell transplantation or in second or subsequent chronic phase

    • No molecular relapse (only evidence is detection of bcr-abl rearrangement with normal bone marrow and blood morphology and normal standard cytogenetic analysis)
  • Stratum III (closed to accrual as of 7/29/05): Newly diagnosed CML in first chronic phase with no prior treatment except hydroxyurea
  • Stratum IV: Newly diagnosed CML in first chronic phase with no prior treatment except hydroxyurea
  • No accelerated or blast phase defined as one or more of the following:

    • WBC doubling time less than 5 days
    • Chloroma
    • Medullary fibrosis
    • More than 10% blasts in peripheral blood or bone marrow
    • More than 20% promyelocytes in peripheral blood or bone marrow
    • More than 20% basophils and eosinophils in peripheral blood

PATIENT CHARACTERISTICS:

Age:

  • Under 22

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 8 weeks

Hematopoietic:

  • See Disease Characteristics
  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram

Hepatic:

  • Bilirubin no greater than 1.5 times normal
  • ALT less than 3.0 times normal
  • Albumin greater than 2 g/dL

Renal:

  • Creatinine no greater than 1.5 times normal OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No CNS toxicity greater than grade 2

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Disease Characteristics
  • No prior immunotherapy (for patients in stratum III [closed to accrual as of 7/29/05] and stratum IV only)
  • At least 3 months since prior stem cell transplantation (SCT) (patients with allogeneic SCT must have no active graft-versus-host disease [GVHD] and have stable use of steroids) (for patients in stratum II only )
  • At least 1 week since prior growth factors
  • At least 1 week since prior biologic therapy, including interferon alfa (for patients in stratum I [closed to accrual as of 12/05/03] and stratum II only)
  • Recovered from prior immunotherapy
  • No concurrent immunomodulating agents

Chemotherapy:

  • See Disease Characteristics
  • No prior chemotherapy (for patients in stratum III [closed to accrual as of 7/29/05] and stratum IV only)
  • At least 6 weeks since prior busulfan or nitrosoureas
  • At least 7 days since prior hydroxyurea
  • At least 7 days since prior low-dose cytarabine (less than 30 mg/m^2 every 12 to 24 hours)
  • At least 14 days since prior moderate-dose cytarabine (100-200 mg/m^2 for 5 to 7 days)
  • At least 28 days since prior high-dose cytarabine (1-3 g/m^2 every 12 to 24 hours for 6 to 12 doses)
  • At least 21 days since all other cytotoxic chemotherapy
  • Recovered from prior chemotherapy
  • No concurrent chemotherapy

Endocrine therapy:

  • No concurrent steroids other than for controlled GVHD in patients with prior allogeneic SCT

Radiotherapy:

  • No prior radiotherapy (for patients in stratum III [closed to accrual as of 7/29/05] and stratum IV only)
  • At least 2 weeks since prior local palliative (small port) radiotherapy*
  • At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of pelvis*
  • At least 6 weeks since prior substantial bone marrow radiotherapy*
  • Recovered from prior radiotherapy NOTE: * For patients in stratum I (closed to accrual as of 12/05/03) and stratum II only

Surgery:

  • Not specified

Other:

  • No prior imatinib mesylate
  • No concurrent enzyme-activating anticonvulsants
  • No concurrent warfarin
  • No concurrent naturopathic agents or herbal medicines
  • No other concurrent investigational agents
  • Concurrent low-molecular weight heparin allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00030394

  Show 97 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Martin Champagne, MD Hopital Sainte Justine
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00030394     History of Changes
Other Study ID Numbers: CDR0000069161, COG-AAML0123
Study First Received: February 14, 2002
Last Updated: June 4, 2011
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
chronic phase chronic myelogenous leukemia
chronic myelogenous leukemia, BCR-ABL1 positive
childhood chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012