- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00511303
Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia
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
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 Overview
Detailed Description
Study Type
Enrollment
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female patients * 18 years of age.
- Patients with Ph chromosome positive CML in the chronic-phase of the disease.
Patients must have documented resistance to an interferon-alpha containing therapy, defined as any of the following:
- Hematologic Resistance - Failure to achieve a complete hematologic response, lasting for at least 1 month despite of 6 or more months of an interferon-alpha containing regimen.
- Cytogenetic Resistance - Bone marrow cytogenetics showing *65% Ph chromosome positivity after at least one year of interferon-alpha based therapy
- Cytogenetic Refractoriness - An increase in the Ph+ chromosome bone marrow cells by at least 30 percentage points (eg., from 20% to 50%, or from 30% to 60%) confirmed by two samples at least 1 month apart, or an increase to * 65%
- Hematologic Refractoriness - A rising WBC count (*100% increase and to a level *20 x 109/L confirmed by two samples taken at least two weeks apart) while receiving an interferon-alpha containing regimen.
- Patients who have demonstrated intolerance to interferon-alpha therapy defined as: a documented * Grade 3 non-hematologic toxicity (grade 2 in case of neurologic or neuropsichiatric toxicity), persisting for more than 2 weeks, in a patient receiving an interferon-alpha containing regimen. Patients who are intolerant to interferon-alpha must be more than 3 months from time of diagnosis.
- Written voluntary informed consent.
Exclusion Criteria:
- Patients of childbearing potential without a negative pregnancy test prior to the initiation of study drug. Barrier contraceptive precautions are to be used throughout the trial in both sexes.
- Serum bilirubin and creatinine concentrations more than twice the upper limit of the normal range.
- SGOT and SGPT more than twice the upper limit of the normal range.
- Percentage of blasts, or basophils in the peripheral blood or bone marrow > 15%.
- Percentage of blasts plus promyelocytes in the peripheral blood or bone marrow ( 30%.
- Patients with a platelet count < 100 x 109/L
- Patients with an ECOG Performance Status Score * 3.
- Patients receiving busulfan within 6 weeks of Visit 1.
- Patients receiving treatment with interferon-alpha within 14 days of Visit 1.
- Patients receiving treatment with cytosine arabinoside within 14 days of Visit 1.
- Patients receiving treatment with hydroxyurea within 7 days of Visit 1.
- Patients who have received other investigational agents within 28 days of Visit 1.
- Patients with Grade 3/4 cardiac problems as defined by the New York Heart Association Criteria.
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.
- Patients who are likely to be submitted to any transplantation procedure during the study period (12 months)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
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.
|
Secondary Outcome Measures
Outcome Measure |
---|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michele Baccarani, MD, Istituto di Ematologia "L e A Seragnoli"-Policlinico S.Orsola-Malpighi di Bologna
Study record dates
Study Major Dates
Study Start
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- CML 002
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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