A Phase III Study of STI571 Versus Interferon-a (IFN-a) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
18 Years
70 Years
Both
Leukemia
Trial Information
A Phase III Study of STI571 Versus Interferon-a (IFN-a) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
OBJECTIVES: I. Compare the time to treatment failure and overall survival in patients with
newly diagnosed, previously untreated, Philadelphia chromosome positive, chronic phase
chronic myelogenous leukemia treated with STI571 vs interferon alfa combined with
cytarabine. II. Compare the quality of life and disease and treatment related toxicities in
patients treated with these 2 regimens. III. Compare the rate and duration of complete
hematologic response (CHR) and major cytogenetic response (MCR) in patients treated with
these 2 regimens. IV. Compare the rate and duration of MCR and CHR attributable to crossover
therapy in patients who crossover to receive STI571 OR interferon alfa combined with
cytarabine. V. Compare the tolerability and safety of these regimens in these patients. VI.
Determine the population pharmacokinetics of STI571 in these patients.
OUTLINE: This is a randomized, open label, crossover, multicenter study. Patients are
randomized to one of two treatment arms: Arm I: Patients receive oral STI571 once daily. Arm
II: Patients receive interferon alfa (IFN-A) subcutaneously (SQ) daily. Gradual intrapatient
dose escalation is performed until the target dose of IFN-A is achieved. Patients then also
receive cytarabine SQ daily for 10 days every month. Cytarabine is discontinued when a
complete cytogenetic response is achieved and confirmed on two consecutive occasions not
more than 3 months apart. Both arms: Courses repeat monthly in the absence of progression to
accelerated phase or blast crisis, or unacceptable toxicity. Patients with no complete
hematologic response at 6 months, no major cytogenetic response at year 2, or loss of
complete hematologic response (without progression to accelerated or blastic phase)
discontinue treatment on the arm to which they were originally randomized and begin
treatment on the other arm. Crossover courses repeat monthly in the absence of progression
to accelerated phase or blast crisis, or unacceptable toxicity. Quality of life is assessed
prior to study; monthly for the first 6 months of study; at 9, 12, 18, and 24 months; at
time of crossover (if applicable); and at treatment discontinuation before year 2 (if
applicable). All patients are followed every 3 months for up to 8 years.
PROJECTED ACCRUAL: A total of 850 patients (425 per arm) will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS: Cytogenetically proven Philadelphia chromosome positive chronic
phase chronic myelogenous leukemia (CML) Initial diagnosis within the past 6 months No
prior chemotherapy, including regimens used in peripheral blood progenitor cell (PBPC)
mobilization for PBPC transplantation, for CML except hydroxyurea Must meet the following
criteria: Blasts in peripheral blood and bone marrow less than 15% Blasts plus
promyelocytes in peripheral blood and bone marrow less than 30% Basophils in peripheral
blood less than 20% Platelet count at least 100,000/mm3 No extramedullary leukemic
involvement except spleen or liver No patient for which a sibling bone marrow donor is
available and allogeneic bone marrow transplantation is elected as first line therapy
PATIENT CHARACTERISTICS: Age: 18 to 70 Performance status: ECOG 0-2 Life expectancy: Not
specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than
1.5 times upper limit of normal (ULN) SGOT and SGPT no greater than 1.5 times (ULN) INR
and PTT no greater than 1.5 times ULN Renal: Creatinine no greater than 1.5 times ULN
Cardiovascular: No angina No New York Heart Association class III or IV heart disease
Other: No uncontrolled medical disease, such as diabetes mellitus, thyroid dysfunction,
neuropsychiatric disorders, or infection HIV negative Not pregnant or nursing Negative
pregnancy test Fertile patients must use effective barrier contraception No other
malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of
the cervix No history of noncompliance with medical regimens or potential for
noncompliance
PRIOR CONCURRENT THERAPY: Biologic therapy: Concurrent leukapheresis allowed during the
first month of study No concurrent allogeneic bone marrow transplantation Concurrent
anagrelide allowed during the first 3 months of study Chemotherapy: See Disease
Characteristics Concurrent hydroxyurea allowed only during the first 3 months of study
Endocrine therapy: No concurrent systemic steroids for more than 2 weeks Radiotherapy: Not
specified Surgery: Greater than 4 weeks since prior major surgery and recovered Other: No
other prior investigational agents No other concurrent investigational drugs
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Ilana Monteleone
Investigator Role:
Study Chair
Investigator Affiliation:
Novartis Pharmaceuticals
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000068089
NCT ID:
NCT00006343
Start Date:
June 2000
Completion Date:
March 2007
Related Keywords:
- Leukemia
- chronic phase chronic myelogenous leukemia
- chronic myelogenous leukemia, BCR-ABL1 positive
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Philadelphia Chromosome
Name | Location |
|---|---|
| Novartis Pharmaceuticals Corporation | East Hanover, New Jersey 07936 |
