Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	Under 22	NCI	COG-AAML0123 AAML0123, NCT00030394

Objectives

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

Entry 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/mm³ 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/mm³) 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

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/m² every 12 to 24 hours)
• At least 14 days since prior moderate-dose cytarabine (100-200 mg/m² for 5 to 7 days)
• At least 28 days since prior high-dose cytarabine (1-3 g/m² 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

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

Expected Enrollment

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.

Outcomes

Response rate
Disease-free survival
Pharmacokinetics
Toxic effects

Rate of hematological, cytogenetic, and molecular responses at 3, 6, and 12 months

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.

Champagne MA, Fu C, Chang M, et al.: Imatinib in children with newly diagnosed chronic phase chronic myelogenous leukemia (CP CML): AAML0123 COG study. [Abstract] Blood 108 (11): A-2140, 2006.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Martin Champagne, MD, Protocol chair		Ph: 514-345-4969

Registry Information
Official Title		A Phase II Study of Gleevec in Ph+ Chronic Phase Chronic Myelogenous Leukemia
Trial Start Date		2002-09-30
Registered in ClinicalTrials.gov		NCT00030394
Date Submitted to PDQ		2002-11-19
Information Last Verified		2006-10-21
NCI Grant/Contract Number		CA13539

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