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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


Phase 3
18 Years
75 Years
Open (Enrolling)
Both
Leukemia

Thank you

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 UCLALos Angeles, California  90095-1781