A Randomized Open-Label Study of 400 mg Versus 800 mg of Gleevec/Glivec (Imatinib Mesylate) in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Using Molecular Endpoints
18 Years
75 Years
Both
Leukemia
Trial Information
A Randomized Open-Label Study of 400 mg Versus 800 mg of Gleevec/Glivec (Imatinib Mesylate) in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Using Molecular Endpoints
OBJECTIVES:
Primary
- Compare the efficacy of 2 different doses of imatinib mesylate, in terms of molecular
response rate at 12 months, in patients with newly diagnosed chronic myelogenous
leukemia in chronic phase (CML-CP).
Secondary
- Compare the rate of hematologic response in these patients.
- Compare the rate of complete cytogenetic response (CCyR) in these patients.
- Compare the time to CCyR, molecular response, and complete molecular response in these
patients.
- Compare the percentage of patients with ≥ 3-log reduction in Bcr-Abl transcripts and
with undetectable levels at 12 months and beyond.
- Compare the progression-free survival at 5 years in these patients.
- Compare the safety profile of 2 different doses of imatinib mesylate in these patients.
- Validate molecular response as a prognostic factor for time to progression in these
patients.
- Compare the quality of life of these patients and healthcare resource utilization.
- Compare the pharmacokinetic characteristics of 2 different doses of imatinib mesylate
in these patients.
- Investigate tumor-specific mutations.
- Assess Bcr-Abl pathway activation, as measured by tyrosine phosphorylation of Bcr-Abl
downstream molecules, including Crk1 and STAT-5.
- Correlate Bcr-Abl transcript and Bcr-Abl pathway activation with clinical response.
- Conduct proteomic and pharmacogenomic analyses to identify potential biomarkers that
may predict the response to imatinib mesylate, markers of imatinib mesylate effect, and
potential markers of toxicity in peripheral blood.
- Compare the actual dose-intensity delivered in patients treated with 2 different doses
of imatinib mesylate.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
according to the Sokal relative risk score (< 0.8 [low-risk] vs 0.8-1.2 [intermediate risk]
vs > 1.2 [high-risk]). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral imatinib mesylate twice daily in the absence of disease
progression or unacceptable toxicity.
- Arm II: Patients receive oral imatinib mesylate once daily in the absence of disease
progression or unacceptable toxicity. Patients with unresponsive disease after 3-12
months of treatment may receive imatinib mesylate twice daily in the absence of disease
progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 3 months during study treatment, and at 6 and
12 months after completion of study treatment.
After completion of study treatment, patients are followed every 3 months for up to 5 years.
PROJECTED ACCRUAL: A total of 420 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Cytogenetically confirmed chronic myelogenous leukemia in chronic phase (CML-CP)
- Philadelphia chromosome (9;22) translocations
- Presence of Bcr-Abl
- Diagnosed within the past 6 months
- Chronic phase is defined by all of the following:
- Less than 15% blasts in peripheral blood and bone marrow
- Less than 30% blasts plus promyelocytes in peripheral blood and bone marrow
- Less than 20% basophils in the peripheral blood
- Platelet count ≥ 100,000/mm³
- No evidence of extramedullary leukemic involvement, with the exception of
hepatosplenomegaly
- No late chronic phase, accelerated phase, or blastic phase CML
- No sibling donor available for allogeneic bone marrow transplantation as first-line
treatment
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Bilirubin < 1.5 times upper limit of normal (ULN)
- SGOT and SGPT < 2.5 times ULN
- Creatinine < 1.5 times ULN
- INR or PTT ≤ 1.5 times ULN except for patients on treatment with oral anticoagulants
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for up to 3
months after completion of study treatment
- No other primary malignancy except if the malignancy is neither currently clinically
significant nor requires active intervention
- No severe or uncontrolled medical condition (i.e., uncontrolled diabetes or chronic
renal disease)
- No known HIV positivity
- No significant history of noncompliance to medical regimens
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior imatinib mesylate except for patients who successfully complete clinical
trial NOVARTIS-CSTI571A2107 immediately prior to entry into this study
- No prior treatment for CML exceeding 1 month in duration with the exception of
hydroxyurea and/or anagrelide
- No prior radiotherapy to ≥ 25% of the bone marrow
- More than 4 weeks since prior major surgery and recovered
- No concurrent grapefruit juice
- No other concurrent investigational agents
- No other concurrent anticancer agents, including chemotherapy or biologic agents
- Concurrent anagrelide during the first month of study treatment allowed
- Concurrent systemic corticosteroids allowed
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of molecular response as measured by log reduction of Bcr-Abl transcript at 12 months and then annually
Safety Issue:
No
Principal Investigator
Ronald Paquette, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000480338
NCT ID:
NCT00324636
Start Date:
January 2006
Completion Date:
Related Keywords:
- Leukemia
- chronic myelogenous leukemia, BCR-ABL1 positive
- chronic phase chronic myelogenous leukemia
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
