Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia
This is a Phase II, open-label, multi-center trial designed primarily to evaluate the rate of complete or major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow, in patients with CML who are refractory to or intolerant of interferon-alpha.
During the core phase of the study, patients will receive once daily oral administration of STI571 at a dose of 400 mg, for up to 12 months. After completing 12 months of therapy patients may be eligible to receive additional therapy provided that, in the opinion of the investigator, the patient has benefited from treatment with STI571 and in the absence of safety concerns. Patients will receive STI571 on an outpatient basis.
During the extended phase (which is of indefinite duration), patients may continue STI571 until either progression to accelerated phase, blast phase, death, the development of intolerable toxicity, or the investigator feels it is no longer in the patient's best interest to continue therapy, whichever comes first. The number of visits will be at a reduced frequency. Patients who discontinue study drug will be followed for survival for up to 5 years.
STI571 will be considered active if the interferon-refractory patient population satisfies the target of achieving a complete or major response at a rate of at least 30%, within the preset error limits. Cytogenetic responses will be evaluated every three months and categorized as either complete (0% Ph+ chromosome cells), or major (1 to 35% Ph+ chromosome cells) responses. STI571 will be discontinued for any patient whose disease progresses to either the accelerated phase or blast crisis.
A minimum of 100 patients who are interferon refractory will receive STI571 administered at a dose of 400 mg once a day. In addition, the protocol is also open for patients who are intolerant to interferon-alpha in order to get a preliminary evaluation of their response to STI571 therapy. Up to 100 intolerant patients will be enrolled. Enrollment of intolerant patients will cease at 100, or whenever the 100 refractory patients are accrued, whichever comes first.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia Who Are Resistant to or Intolerant of *-Interferon. A Phase II Study|
- To determine the rate of complete and major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow, in patients with CML who are refractory to interferon-alpha.
- To quantify the molecular response of STI571 as demonstrated by a decrease of bcr/abl transcript in peripheral blood cells,
- To determine the rate and duration of complete hematological response,
- To evaluate the duration of complete and major cytogenetic responses,
- To evaluate the safety profile and improvement of symptomatic parameters,
- To evaluate the time to accelerated disease, or blast crisis,
- To evaluate overall survival,
- To evaluate the rate and the duration of hematologic and cytogenetic response in patients intolerant to interferon-alpha
|Study Start Date:||August 2000|
This Phase II trial will evaluate at least 100 patients for the rate of complete or major cytogenetic response of STI571 as demonstrated by a decrease in the percentage of Ph chromosome positive cells in the bone marrow in patients with CML who are refractory to or intolerant of interferon-alpha. Statistical considerations are based on the refractory patient population only. Intolerant patients are included as long as recruitment of the refractory patients is ongoing, up to a maximum of 100 intolerant patients, whichever comes first.