Leukemia
Conditions
Keywords
chronic phase chronic myelogenous leukemia, Philadelphia chromosome positive chronic myelogenous leukemia
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. 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 giving imatinib mesylate together with cytarabine to see how well it works in treating patients with chronic phase chronic myelogenous leukemia.
Detailed description
OBJECTIVES: * Determine the rate and duration of complete or major and minor cytogenetic responses after 6 and 12 months of treatment in patients with chronic phase chronic myelogenous leukemia treated with imatinib mesylate and cytarabine. * Determine the rate and duration of complete hematologic responses after 6 and 12 months of treatment in patients treated with this regimen. * Determine the rate of molecular response in patients with a complete cytogenetic response after 6 and 12 months of treatment with this regimen. * Determine the pharmacokinetics of this regimen in these patients. * Determine the safety of this regimen in these patients. OUTLINE: This is a nonrandomized, open-label, multicenter study. Patients receive oral imatinib mesylate on days 1-28 and cytarabine subcutaneously on days 15-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients are followed for 30-60 days. PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.
Interventions
DRUGcytarabine
Once daily subcutaneous injection of Ara-C (Cytarabine) at a dose of 20 mg (10 mg or 5 mg if they have been dose reduced) per square meter of calculated body surface area, on days 15-28 of each sequential 28 day cycle
DRUGimatinib mesylate
Once daily oral administration of STI571 (Imatinib Mesylate) at a dose of 400 mg for 12 months.
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Cytogenetically confirmed chronic phase chronic myelogenous leukemia (CML) * Less than 15% blasts in peripheral blood or bone marrow * Less than 30% blasts and promyelocytes in peripheral blood or bone marrow * Less than 20% basophils in blood or bone marrow * Platelet count at least 100,000/mm\^3 * Philadelphia chromosome positive * No more than 6 months since initial diagnosis * No presence of leukemia beyond the bone marrow, blood, liver, or spleen (i.e., chloroma) * Refused allogeneic stem cell transplantation as first-line therapy PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * AST or ALT no greater than 2 times ULN Renal: * Creatinine no greater than 1.5 times ULN Cardiovascular: * No New York Heart Association class III or IV heart disease Other: * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for at least 3 months after study participation * No other serious uncontrolled medical condition * No history of noncompliance to medical regimens or potential unreliability PRIOR CONCURRENT THERAPY: Biologic therapy: * See Disease Characteristics * No prior biologic therapy for CML Chemotherapy: * No prior chemotherapy for CML except hydroxyurea * Concurrent hydroxyurea to control blood counts during first 3 months of treatment allowed * No other concurrent chemotherapy Endocrine therapy: * No prior endocrine therapy for CML Radiotherapy: * No prior radiotherapy for CML Surgery: * Not specified Other: * More than 28 days since prior investigational anticancer agents * Prior anagrelide hydrochloride for CML allowed * Concurrent anagrelide hydrochloride to control blood counts during first 3 months of treatment allowed * No concurrent grapefruit juice or grapefruit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of Major Cytogenetic Response at 6 Months | 6 months | Cytogenetic response is defined in terms of the percentage of Philadelphia (Ph) chromosome. Major cytogenetic response is defined as 0-34% Ph-positive cells. |
Secondary
| Measure | Time frame |
|---|---|
| The Rate of Complete Cytogenetic Response at 6 Months | 6 months |
| The Rate of Complete and Major Cytogenetic Responses at 12 Months | 12 months |
| The Rate of Minor Cytogenetic Responses at 6 and 12 Months | 6 and 12 months |
| The Rate of Complete Hematologic Responses at 6 and 12 Months | 6 and 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cytarabine/ Imatinib Mesylate Cytarabine: Once daily subcutaneous injection of Ara-C (Cytarabine) at a dose of 20 mg (10 mg or 5 mg if they have been dose reduced) per square meter of calculated body surface area, on days 15-28 of each sequential 28 day cycle
Imatinib Mesylate: Once daily oral administration of STI571 (Imatinib Mesylate) at a dose of 400 mg for 12 months | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Cytarabine/ Imatinib Mesylate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 24 |
| serious Total, serious adverse events | 13 / 24 |
Outcome results
Primary
The Rate of Major Cytogenetic Response at 6 Months
Cytogenetic response is defined in terms of the percentage of Philadelphia (Ph) chromosome. Major cytogenetic response is defined as 0-34% Ph-positive cells.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cytarabine/ Imatinib Mesylate | The Rate of Major Cytogenetic Response at 6 Months | 5 Participants |
Secondary
The Rate of Complete and Major Cytogenetic Responses at 12 Months
Time frame: 12 months
Secondary
The Rate of Complete Cytogenetic Response at 6 Months
Time frame: 6 months
Secondary
The Rate of Complete Hematologic Responses at 6 and 12 Months
Time frame: 6 and 12 months
Secondary
The Rate of Minor Cytogenetic Responses at 6 and 12 Months
Time frame: 6 and 12 months