Back to resultsProtein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia
Primary Purpose
Chronic Myeloid Leukemia
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
STI571
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Philadelphia chromosome, protein-tyrosine kinases
Eligibility Criteria
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)
Sites / Locations
Outcomes
Primary Outcome Measures
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
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
Full Information
NCT ID
NCT00511303
First Posted
August 2, 2007
Last Updated
August 2, 2007
Sponsor
University of Bologna
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT00511303
Brief Title
Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2007
Overall Recruitment Status
Completed
Study Start Date
August 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of Bologna
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
Philadelphia chromosome, protein-tyrosine kinases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
200 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
STI571
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
To quantify the molecular response of STI571 as demonstrated by a decrease of bcr/abl transcript in peripheral blood cells,
Title
To determine the rate and duration of complete hematological response,
Title
To evaluate the duration of complete and major cytogenetic responses,
Title
To evaluate the safety profile and improvement of symptomatic parameters,
Title
To evaluate the time to accelerated disease, or blast crisis,
Title
To evaluate overall survival,
Title
To evaluate the rate and the duration of hematologic and cytogenetic response in patients intolerant to interferon-alpha
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Baccarani, MD
Organizational Affiliation
Istituto di Ematologia "L e A Seragnoli"-Policlinico S.Orsola-Malpighi di Bologna
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Protein-Tyrosine Kinase Inhibitor (STI571) for Treatment of Patients With Ph+ Chronic Myeloid Leukemia
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