Leukemia, Myelogenous, Chronic, BCR-ABL PositivePhase 2NCT00171223
An Extension Study to Determine the Efficacy and Safety of STI571 in Participants With Chronic Myeloid Leukemia Who Are Refractory to or Intolerant of Interferon-Alpha
A Phase 2 study testing STI571 in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive, run by Novartis Pharmaceuticals at 28 sites in 6 countries.
Trial summary
During the Core Phase of the study, participants received STI571 at a dose of 400 milligrams (mg) daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study provided that, in the opinion of the investigator, they had benefited from… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- What is being tested?
- STI571
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 532 participants
- Where
- 28 sitesin 6 countries
- Study dates
- 6 Dec 1999to 29 Nov 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants included in the study were:
- Consenting males or females greater than or equal to (≥)18 years of age with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML).
- With a documented failure of interferon-alpha (IFN) or an IFN-containing therapy, characterized as resistance or refractoriness defined as any of the following:
- Hematologic Resistance - Failure to achieve a complete hematological response (CHR), lasting for at least 1 month despite 6 or more months of IFN or an IFN-containing regimen, in which IFN was administered at a dose of at least 25 million international units (MIU) per week. During this treatment period the cumulative duration of hydroxyurea therapy may not have exceeded 50% of the treatment period with the IFN-containing regimen.
- Cytogenetic Resistance - Bone marrow cytogenetics showing ≥65% Ph+ after one year of IFN-based therapy,
- Cytogenetic Refractoriness - An increase in the Ph+ chromosome in BM cells by at least 30 percentage points (e.g. from 20% to 50%, or from 30% to 60%) confirmed by two samples at least 1 month apart, or an absolute increase to ≥65%,
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- Hematologic Refractoriness - A rising white blood cell count (WBC) [to a level ≥20 x 10^9/L confirmed by two samples taken at least two weeks apart] for participants achieving a complete hematologic response while receiving IFN or an IFN-containing regimen. This regimen must have included IFN at a dose of at least 25 MIU administered per week. During this treatment period the cumulative duration of hydroxyurea therapy may not have exceeded 50% of the treatment period with the IFN-containing regimen.
- In this report all refractory populations were referred to as "relapsed" populations.
- With a documented intolerance to IFN therapy defined as a ≥Grade 3 non-hematologic toxicity persisting for at least one month, for participants receiving IFN or an IFN- containing regimen. IFN was to be administered at a dose of at least 25 MIU/week. Participants who were intolerant of IFN were to have been diagnosed ≥6 months prior to the time of entry into the study.
Who cannot join
- Participants excluded from the study were:
- Females of childbearing potential without a negative pregnancy test prior to the initiation of study drug. Barrier contraceptive precautions were to be used throughout the trial in both sexes.
- With serum bilirubin and creatinine concentrations more than twice the upper limit of the normal range (ULN).
- With serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) more than twice the ULN.
- With >15% of blasts or basophils in peripheral blood (PB) or bone marrow (BM).
- With ≥30% of blasts plus promyelocytes in PB or BM.
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- With a platelet count of less than (<)100 x 10^9/L.
- With an Eastern Cooperative Oncology Group (ECOG) Performance Status Score ≥3.
- Receiving busulfan within 6 weeks of Day 1.
- Receiving treatment with IFN or cytosine arabinoside (Ara-C) within 14 days of Day 1.
- Receiving treatment with hydroxyurea within 7 days of Day 1.
- Receiving other investigational agents within 28 days of Day 1.
- With prior marrow or stem cell transplantation.
Trial locations and contacts
28 sites in 6 countries.
28 sites in 6 countries
United States11 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins Oncology Center
Baltimore, Maryland, 21231
Dana Faber Cancer Institute
Boston, Massachusetts, 02115
Northwestern Univ meical School/Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, 60611
Wayne State University/Kamanos Cancer Center
Detroit, Michigan, 48201
MD Anderson Cancer Center, University of Texas
Houston, Texas, 77030
UCLA Medical Center
Los Angeles, California, 90095
New York Presbyterian Hospital
New York, New York, 10021
Oregon Health & sciences University
Portland, Oregon, 97239
C/O V. Ward - Washington Univ. school of Medicine
St Louis, Missouri, 63110
H. Lee Moffet Cancer Center & Research Institute/Univ of South Florida
Tampa, Florida, 33612
Italy7 sites
Novartis Investigative Site
Bologna
Novartis Investigative Site
Milan
Novartis Investigative Site
Monza
Novartis Investigative Site
Orbassano
Novartis Investigative Site
Pavia
Novartis Investigative Site
Rome
Novartis Investigative Site
Udine
Germany4 sites
Novartis Investigative Site
Frankfurt
Novartis Investigative Site
Leipzig
Novartis Investigative Site
Mainz
Novartis Investigative Site
Mannheim
France3 sites
Novartis Investigative Site
Lille
Novartis Investigative Site
Pessac
Novartis Investigative Site
Poitiers
United Kingdom2 sites
Novartis Investigative Site
London
Novartis Investigative Site
Newcastle upon Tyne
About this study
Official title: An Extension to a Phase II Study to Determine the Efficacy and Safety of STI571 in Patients With Chronic Myeloid Leukemia Who Are Refractory to or Intolerant of Interferon-Alpha
During the Core Phase of the study, participants received STI571 at a dose of 400 milligrams (mg) daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study provided that, in the opinion of the investigator, they had benefited from treatment with STI571 and there were no safety concerns.
- Being tested
- STI571
- Keywords
- Chronic Myelogenous Leukemia, CML, Philadelphia Chromosome, Accelerated phase, Acute Myelogenous Leukemia, AML, Acute Lymphoblastic Leukemia, ALL, Imatinib mesylate
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Philadelphia Chromosome, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STI571Drug
Also called Imatinib Mesylate
STI571 oral capsules or tablets.
| Study group | Role | What they receive |
|---|---|---|
| All Participants With Chronic Myeloid Leukemia | Experimental | Participants received STI571, capsules or tablets, orally, once a day at a dose of 400 mg. During the Core Phase of the study, participants received STI571 daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study, and they continued STI571 for as long as the therapy was beneficial or until death, intolerable toxicity or the decision to discontinue by the investigator, whichever came first. (Maximum duration on study was approximately 14 years). Receives: Drug: STI571 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571
Response was evaluated from bone marrow aspirates and biopsy samples. Bone marrow cytogenetic studies were performed every 3 months during the core phase of the study, then twice yearly, then annually to evaluate Philadelphia chromosome positive (Ph+). Cytogenetic response was defined as the best response the participant achieved during study. Based on the percentage of Ph+ cells = (positive cells/ examined cells) x100, at each BM assessment the cytogenetic response was classified as: Complete Cytogenetic Response (CCyR):, 0% Ph+ cells; Partial Cytogenetic Response (PCyR):, >0 - 35% Ph+ cells; Minor: >35 - 65% Ph+ cells; and Minimal: >65 - 95% Ph+ cells, None: >95 % Ph+ cells and Not done: <20 metaphases were examined and/or response could not be assigned. Major Cytogenetic Response (MCyR) was defined as sum of the CCyR plus PCyR rates.
Measured: Up to 6 years after the start of treatment
Secondary outcomes (6)
Percentage of Participants With Complete Hematologic Response to STI571
Hematologic response was evaluated from hematology measurements in the peripheral blood. Complete hematological response was defined as normalization of peripheral blood counts [WBC and platelet count < upper limit of normal (ULN) at the laboratory where the analysis was performed], with a normal WBC differential, and no immature granulocytes present, lasting for 4 weeks.
Measured: 12 months after the start of treatment
Duration of Complete Hematologic Response to STI571
Duration of hematologic response was defined as the time from the first documentation of the complete hematologic response to the date the loss of complete hematologic response is documented. Loss of complete hematological response was defined as a rising WBC count (increased to a level above the ULN at the laboratory where the analysis was performed confirmed by two samples obtained one month apart). The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time. Complete hematological response was defined as normalization of peripheral blood counts (WBC and platelet count < ULN at the laboratory where the analysis was performed), with a normal WBC differential, and no immature granulocytes present, lasting for 4 weeks.
Measured: 12 months after the start of treatment
Time to Complete Hematologic Response to STI571
Time to Complete Hematologic Response was defined for all participants with calculated confirmed complete hematologic response as the time until first documented response (which was confirmed >= 4 weeks). Complete hematological response was defined as normalization of peripheral blood counts (WBC and platelet count < ULN at the laboratory where the analysis was performed), with a normal WBC differential, and no immature granulocytes present, lasting for 4 weeks.
Measured: 12 months after the start of treatment
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms
National Cancer Institute (NCI)/ National Institute of Health (NIH) provides a grading (severity) scale for each adverse event (AE) term, the Common Toxicity Criteria (CTC). Grade 3 refers to severe AE and Grade 4 refers to life-threatening or disabling AE. Cancer-related symptoms included fever, night sweats, bone pain, arthralgia, abdominal discomfort, fatigue and anorexia.
Measured: Up to 9 months after the start of treatment
Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status
The ECOG performance status was recorded at baseline and every 3 months during the core study. The ECOG Performance Scale has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair.
Measured: Up to 9 months after the start of treatment
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates
Overall survival was defined as the time from the first dose of STI571 to the death of the participant. If a participant is not known to have died, survival was censored at the time of last contact. Kaplan-Meier estimates of the percentage of participants at each time point was calculated.
Measured: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 and 156 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study start6 Dec 1999
- Primary completion29 Nov 2013
- Study completion29 Nov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Myelogenous, Chronic, BCR-ABL PositiveStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 532 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00171223
- Sponsor's protocol ID
- CSTI571A0110E2
- Other IDs
- 2005-001382-33, 2005
- Status last verified
- Jul 2021
- First submitted
- 12 Sep 2005
- Last updated
- 22 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Extension to a Phase II Study to Determine the Efficacy and Safety of STI571 in Patients With Chronic Myeloid Leukemia Who Are Refractory to or Intolerant of Interferon-Alpha
- ClinicalTrials.gov ID
- NCT00171223
- Acronym / sponsor ID
- CSTI571A0110E2
- Keywords
- Chronic Myelogenous Leukemia, CML, Philadelphia Chromosome, Accelerated phase, Acute Myelogenous Leukemia, AML, Acute Lymphoblastic Leukemia, ALL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 532 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 6 Dec 1999 (actual)
- Primary completion
- 29 Nov 2013 (actual)
- Study completion
- 29 Nov 2013 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 22 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
During the Core Phase of the study, participants received STI571 at a dose of 400 milligrams (mg) daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study provided that, in the opinion of the investigator, they had benefited from treatment with STI571 and there were no safety concerns.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Participants With Chronic Myeloid Leukemia | Experimental | Drug: STI571Participants received STI571, capsules or tablets, orally, once a day at a dose of 400 mg. During the Core Phase of the study, participants received STI571 daily for up to 12 months. Participants completing 12 months of therapy were eligible to continue treatment in the Extension Phase of the study, and they continued STI571 for as long as the therapy was beneficial or until death, intolerable toxicity or the decision to discontinue by the investigator, whichever came first. (Maximum duration on study was approximately 14 years). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Consenting males or females greater than or equal to (≥)18 years of age with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML).
- With a documented failure of interferon-alpha (IFN) or an IFN-containing therapy, characterized as resistance or refractoriness defined as any of the following:
- In this report all refractory populations were referred to as "relapsed" populations.
- With a documented intolerance to IFN therapy defined as a ≥Grade 3 non-hematologic toxicity persisting for at least one month, for participants receiving IFN or an IFN- containing regimen. IFN was to be administered at a dose of at least 25 MIU/week. Participants who were intolerant of IFN were to have been diagnosed ≥6 months prior to the time of entry into the study.
Key exclusion criteria (13 listed)
- Females of childbearing potential without a negative pregnancy test prior to the initiation of study drug. Barrier contraceptive precautions were to be used throughout the trial in both sexes.
- With serum bilirubin and creatinine concentrations more than twice the upper limit of the normal range (ULN).
- With serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) more than twice the ULN.
- With >15% of blasts or basophils in peripheral blood (PB) or bone marrow (BM).
- With ≥30% of blasts plus promyelocytes in PB or BM.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| STI571Also: Imatinib MesylateSTI571 oral capsules or tablets. | Drug | All Participants With Chronic Myeloid Leukemia |
Primary outcome
Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571
Time frame: Up to 6 years after the start of treatment
Response was evaluated from bone marrow aspirates and biopsy samples. Bone marrow cytogenetic studies were performed every 3 months during the core phase of the study, then twice yearly, then annually to evaluate Philadelphia chromosome positive (Ph+). Cytogenetic response was defined as the best response the participant achieved during study. Based on the percentage of Ph+ cells = (positive cells/ examined cells) x100, at each BM assessment the cytogenetic response was classified as: Complete Cytogenetic Response (CCyR):, 0% Ph+ cells; Partial Cytogenetic Response (PCyR):, >0 - 35% Ph+ cells; Minor: >35 - 65% Ph+ cells; and Minimal: >65 - 95% Ph+ cells, None: >95 % Ph+ cells and Not done: <20 metaphases were examined and/or response could not be assigned. Major Cytogenetic Response (MCyR) was defined as sum of the CCyR plus PCyR rates.
6 secondary outcomes
Percentage of Participants With Complete Hematologic Response to STI571
Time frame: 12 months after the start of treatment
Duration of Complete Hematologic Response to STI571
Time frame: 12 months after the start of treatment
Time to Complete Hematologic Response to STI571
Time frame: 12 months after the start of treatment
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms
Time frame: Up to 9 months after the start of treatment
Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status
Time frame: Up to 9 months after the start of treatment
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates
Time frame: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 and 156 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
28 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing STI571 in people with Leukemia, Myelogenous, Chronic, BCR-ABL Positive, run by Novartis Pharmaceuticals at 28 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Italy, Germany, France, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 (time frame: Up to 6 years after the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2021.