Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Conditions
Keywords
Chronic Myelogenous Leukemia, CML, Philadelphia Chromosome, Accelerated phase, Acute Myelogenous Leukemia, AML, Acute Lymphoblastic Leukemia, ALL, Imatinib mesylate
Brief 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 treatment with STI571 and there were no safety concerns.
Interventions
DRUGSTI571
STI571 oral capsules or tablets.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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%, * 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.
Exclusion criteria
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Complete Hematologic Response to STI571 | 12 months after the start of treatment | 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. |
| Time to Complete Hematologic Response to STI571 | 12 months after the start of treatment | 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. |
| Percentage of Participants With Complete Hematologic Response to STI571 | 12 months after the start of treatment | 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. |
| Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Up to 9 months after the start of treatment | 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. |
| Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 and 156 months | 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. |
| Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Up to 9 months after the start of treatment | 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. |
Countries
France, Germany, Italy, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hematologic Failure Participants failed to achieve a complete hematologic response, defined as lasting for at least 1 month despite 6 or more months of an interferon-alpha containing regimen, or had a rising WBC (to a level 20 x 10\^9/L) confirmed by two samples taken at least two weeks apart after achieving a complete hematological response while receiving an interferon- alpha containing regimen of at least 25 MIU per week. 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). | 152 |
| Cytogenetic Failure Participants' BM cytogenetics showed \>= 65% Philadelphia chromosome positivity after one year of an interferon-alpha containing regimen or an increase in the Philadelphia chromosome positive 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 increase to \>= 65%. 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). | 188 |
| Interferon-alpha Intolerance Participants demonstrated intolerance to interferon-alpha therapy defined as a documented \> Grade 3 nonhematologic toxicity persisting for more than 1 month after receiving an interferon-alpha containing regimen of at least 25 MIU/week. Participants must have been more than 6 months from time of diagnosis. 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). | 192 |
| Total | 532 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal Laboratory Value (s) | 4 | 2 | 3 |
| Overall Study | Abnormal Procedure | 1 | 0 | 0 |
| Overall Study | Administrative Problems | 4 | 7 | 6 |
| Overall Study | Adverse Event (Non-fatal) | 6 | 5 | 19 |
| Overall Study | Adverse Event (Serious Fatal) | 6 | 8 | 9 |
| Overall Study | Lost to Follow-up | 5 | 2 | 3 |
| Overall Study | No Longer Requires Study Drug (Bone Marrow Transplant) | 2 | 4 | 2 |
| Overall Study | Not Specified (No Data Collected After Cut-off) | 41 | 47 | 58 |
| Overall Study | Participant Withdrew Consent | 12 | 21 | 15 |
| Overall Study | Protocol Violation | 2 | 2 | 3 |
| Overall Study | Unsatisfactory Therapeutic Effect | 57 | 43 | 52 |
Baseline characteristics
| Characteristic | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance | Total |
|---|---|---|---|---|
| Age, Continuous | 55.5 years | 53.0 years | 59.0 years | 57.0 years |
| Age, Customized >= 50 to <= 60 years | 38 Participants | 65 Participants | 50 Participants | 153 Participants |
| Age, Customized >= 60 to <= 70 years | 47 Participants | 44 Participants | 68 Participants | 159 Participants |
| Age, Customized >= 70 years | 10 Participants | 15 Participants | 27 Participants | 52 Participants |
| Age, Customized Less than (<) 50 years | 57 Participants | 64 Participants | 47 Participants | 168 Participants |
| Sex: Female, Male Female | 50 Participants | 77 Participants | 94 Participants | 221 Participants |
| Sex: Female, Male Male | 102 Participants | 111 Participants | 98 Participants | 311 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 13 / 532 |
Outcome results
Primary
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.
Time frame: Up to 6 years after the start of treatment
Population: Intent-To-Treat (ITT) population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematologic Failure | Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | Complete Cytogenetic Response | 29.6 percentage of participants |
| Hematologic Failure | Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | Major Cytogenetic Response | 45.4 percentage of participants |
| Cytogenetic Failure | Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | Complete Cytogenetic Response | 37.2 percentage of participants |
| Cytogenetic Failure | Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | Major Cytogenetic Response | 63.8 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | Complete Cytogenetic Response | 45.8 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 | Major Cytogenetic Response | 65.6 percentage of participants |
Secondary
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.
Time frame: 12 months after the start of treatment
Population: ITT population included all enrolled participants. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hematologic Failure | Duration of Complete Hematologic Response to STI571 | 19.3672 months | Standard Error 0.6383 |
| Cytogenetic Failure | Duration of Complete Hematologic Response to STI571 | 23.9389 months | Standard Error 0.506 |
| Interferon-alpha Intolerance | Duration of Complete Hematologic Response to STI571 | 24.6818 months | Standard Error 0.6507 |
Secondary
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.
Time frame: Up to 9 months after the start of treatment
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Arthralgia Grade 3 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fever Grade 3 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Arthralgia Grade 4 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Bone Pain Grade 4 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Abdominal Discomfort Grade 3 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Bone Pain Grade 3 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Anorexia Grade 3 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fever Grade 4 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fatigue Grade 4 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Abdominal Discomfort Grade 4 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Night Sweats Grade 3 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fatigue Grade 3 | 1 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Anorexia Grade 4 | 0 Participants |
| Hematologic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Night Sweats Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fever Grade 3 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fever Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Night Sweats Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Abdominal Discomfort Grade 3 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Abdominal Discomfort Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Anorexia Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Arthralgia Grade 3 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Anorexia Grade 3 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Arthralgia Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Bone Pain Grade 3 | 1 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Bone Pain Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fatigue Grade 3 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fatigue Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Night Sweats Grade 3 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Bone Pain Grade 3 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fever Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Bone Pain Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Anorexia Grade 3 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Night Sweats Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fatigue Grade 3 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Abdominal Discomfort Grade 3 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Night Sweats Grade 3 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Anorexia Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Arthralgia Grade 3 | 1 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fatigue Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Arthralgia Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Abdominal Discomfort Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms | Fever Grade 3 | 0 Participants |
Secondary
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.
Time frame: Up to 9 months after the start of treatment
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hematologic Failure | Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Grade 3 | 1 Participants |
| Hematologic Failure | Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Grade 4 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Grade 3 | 0 Participants |
| Cytogenetic Failure | Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Grade 4 | 0 Participants |
| Interferon-alpha Intolerance | Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status | Grade 3 | 0 Participants |
Secondary
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.
Time frame: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 and 156 months
Population: ITT population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 84 Months | 68.5 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 120 Months | 61 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 156 Months | 55.5 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 24 Months | 88.1 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 144 Months | 57 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 48 Months | 78.4 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 12 Months | 94.7 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 72 Months | 70.1 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 36 Months | 84 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 132 Months | 59.7 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 96 Months | 66.5 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 108 Months | 63.3 percentage of participants |
| Hematologic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 60 Months | 73.3 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 36 Months | 91.5 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 12 Months | 98.9 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 60 Months | 83.8 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 72 Months | 79.7 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 108 Months | 78.4 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 144 Months | 73.8 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 24 Months | 93.6 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 48 Months | 87.1 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 84 Months | 79.7 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 96 Months | 79.1 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 120 Months | 77 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 132 Months | 75.4 percentage of participants |
| Cytogenetic Failure | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 156 Months | 70.1 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 60 Months | 73.6 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 96 Months | 65.9 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 144 Months | 60.8 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 12 Months | 97.4 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 120 Months | 63.8 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 84 Months | 67.2 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 156 Months | 60.8 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 36 Months | 83.8 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 24 Months | 89.5 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 132 Months | 62.3 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 48 Months | 76.3 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 72 Months | 71.4 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates | 108 Months | 65.3 percentage of participants |
Secondary
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.
Time frame: 12 months after the start of treatment
Population: ITT population included all enrolled participants. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hematologic Failure | Percentage of Participants With Complete Hematologic Response to STI571 | 94.1 percentage of participants |
| Cytogenetic Failure | Percentage of Participants With Complete Hematologic Response to STI571 | 97.9 percentage of participants |
| Interferon-alpha Intolerance | Percentage of Participants With Complete Hematologic Response to STI571 | 91.7 percentage of participants |
Secondary
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.
Time frame: 12 months after the start of treatment
Population: ITT population included all enrolled participants. Here, overall number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hematologic Failure | Time to Complete Hematologic Response to STI571 | 1.64 months |
| Cytogenetic Failure | Time to Complete Hematologic Response to STI571 | 0.72 months |
| Interferon-alpha Intolerance | Time to Complete Hematologic Response to STI571 | 0.72 months |