Trial Outcomes & Findings for 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 (NCT NCT00171223)

Last Updated: 2021-07-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

532 participants

Primary outcome timeframe

Up to 6 years after the start of treatment

Results posted on

2021-07-22

Participant Flow

Participant milestones

Participant milestones
Measure	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 white blood cell count (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 million international units (MIU) per week. Participants received STI571, capsules or tablets, orally, once a day at a dose of 400 milligrams (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).	Cytogenetic Failure Participants' bone marrow (BM) cytogenetics showed greater than or equal to (\>=) 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).	Interferon-alpha Intolerance Participants demonstrated intolerance to interferon-alpha therapy defined as a documented greater than (\>) 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).
Overall Study STARTED	152	188	192
Overall Study COMPLETED	12	47	22
Overall Study NOT COMPLETED	140	141	170

Reasons for withdrawal

Reasons for withdrawal
Measure	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 white blood cell count (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 million international units (MIU) per week. Participants received STI571, capsules or tablets, orally, once a day at a dose of 400 milligrams (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).	Cytogenetic Failure Participants' bone marrow (BM) cytogenetics showed greater than or equal to (\>=) 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).	Interferon-alpha Intolerance Participants demonstrated intolerance to interferon-alpha therapy defined as a documented greater than (\>) 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).
Overall Study Adverse Event (Non-fatal)	6	5	19
Overall Study Abnormal Laboratory Value (s)	4	2	3
Overall Study Abnormal Procedure	1	0	0
Overall Study Unsatisfactory Therapeutic Effect	57	43	52
Overall Study No Longer Requires Study Drug (Bone Marrow Transplant)	2	4	2
Overall Study Protocol Violation	2	2	3
Overall Study Participant Withdrew Consent	12	21	15
Overall Study Lost to Follow-up	5	2	3
Overall Study Administrative Problems	4	7	6
Overall Study Adverse Event (Serious Fatal)	6	8	9
Overall Study Not Specified (No Data Collected After Cut-off)	41	47	58

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hematologic Failure n=152 Participants 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).	Cytogenetic Failure n=188 Participants 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).	Interferon-alpha Intolerance n=192 Participants 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).	Total n=532 Participants Total of all reporting groups
Age, Continuous	55.5 years n=5 Participants	53.0 years n=7 Participants	59.0 years n=5 Participants	57.0 years n=4 Participants
Age, Customized Less than (<) 50 years	57 Participants n=5 Participants	64 Participants n=7 Participants	47 Participants n=5 Participants	168 Participants n=4 Participants
Age, Customized >= 50 to <= 60 years	38 Participants n=5 Participants	65 Participants n=7 Participants	50 Participants n=5 Participants	153 Participants n=4 Participants
Age, Customized >= 60 to <= 70 years	47 Participants n=5 Participants	44 Participants n=7 Participants	68 Participants n=5 Participants	159 Participants n=4 Participants
Age, Customized >= 70 years	10 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants	52 Participants n=4 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	77 Participants n=7 Participants	94 Participants n=5 Participants	221 Participants n=4 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	111 Participants n=7 Participants	98 Participants n=5 Participants	311 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 6 years after the start of treatment

Population: Intent-To-Treat (ITT) population included all enrolled participants.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=152 Participants 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).	Cytogenetic Failure n=188 Participants 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).	Interferon-alpha Intolerance n=192 Participants 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).
Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 Complete Cytogenetic Response	29.6 percentage of participants Interval 22.5 to 37.5	37.2 percentage of participants Interval 30.3 to 44.6	45.8 percentage of participants Interval 38.6 to 53.2
Percentage of Participants With Cytogenetic Response (Complete Cytogenetic Response and Major Cytogenetic Response) to STI571 Major Cytogenetic Response	45.4 percentage of participants Interval 37.3 to 53.7	63.8 percentage of participants Interval 56.5 to 70.7	65.6 percentage of participants Interval 58.4 to 72.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=143 Participants 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).	Cytogenetic Failure n=184 Participants 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).	Interferon-alpha Intolerance n=176 Participants 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).
Percentage of Participants With Complete Hematologic Response to STI571	94.1 percentage of participants Interval 89.1 to 97.3	97.9 percentage of participants Interval 94.6 to 99.4	91.7 percentage of participants Interval 86.8 to 95.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=143 Participants 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).	Cytogenetic Failure n=184 Participants 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).	Interferon-alpha Intolerance n=176 Participants 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).
Duration of Complete Hematologic Response to STI571	19.3672 months Standard Error 0.6383	23.9389 months Standard Error 0.506	24.6818 months Standard Error 0.6507

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=143 Participants 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).	Cytogenetic Failure n=184 Participants 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).	Interferon-alpha Intolerance n=176 Participants 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).
Time to Complete Hematologic Response to STI571	1.64 months Interval 0.6 to 2.8	0.72 months Interval 0.3 to 2.8	0.72 months Interval 0.3 to 2.8

SECONDARY outcome

Timeframe: Up to 9 months after the start of treatment

Population: ITT population included all enrolled participants.

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.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=152 Participants 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).	Cytogenetic Failure n=188 Participants 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).	Interferon-alpha Intolerance n=192 Participants 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).
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Night Sweats Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Abdominal Discomfort Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Abdominal Discomfort Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Anorexia Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Anorexia Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Arthralgia Grade 3	0 Participants	0 Participants	1 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Arthralgia Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Bone Pain Grade 3	0 Participants	1 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Bone Pain Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Fatigue Grade 3	1 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Fatigue Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Fever Grade 3	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Fever Grade 4	0 Participants	0 Participants	0 Participants
Number of Participants With Common Toxicity Criteria Grade 3 or 4 Cancer-related Symptoms Night Sweats Grade 4	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 9 months after the start of treatment

Population: ITT population included all enrolled participants.

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.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=152 Participants 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).	Cytogenetic Failure n=188 Participants 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).	Interferon-alpha Intolerance n=192 Participants 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).
Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 3	1 Participants	0 Participants	0 Participants
Number of Participants With Grade 3 or 4 Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 4	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144 and 156 months

Population: ITT population included all enrolled participants.

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.

Outcome measures

Outcome measures
Measure	Hematologic Failure n=152 Participants 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).	Cytogenetic Failure n=188 Participants 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).	Interferon-alpha Intolerance n=192 Participants 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).
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 48 Months	78.4 percentage of participants Interval 70.9 to 84.2	87.1 percentage of participants Interval 81.4 to 91.2	76.3 percentage of participants Interval 69.6 to 81.7
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 12 Months	94.7 percentage of participants Interval 89.8 to 97.3	98.9 percentage of participants Interval 95.8 to 99.7	97.4 percentage of participants Interval 93.9 to 98.9
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 24 Months	88.1 percentage of participants Interval 81.8 to 92.3	93.6 percentage of participants Interval 89.0 to 96.3	89.5 percentage of participants Interval 84.3 to 93.1
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 36 Months	84 percentage of participants Interval 77.1 to 89.0	91.5 percentage of participants Interval 86.5 to 94.7	83.8 percentage of participants Interval 77.7 to 88.3
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 60 Months	73.3 percentage of participants Interval 65.2 to 79.7	83.8 percentage of participants Interval 77.6 to 88.4	73.6 percentage of participants Interval 66.7 to 79.3
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 72 Months	70.1 percentage of participants Interval 61.9 to 76.9	79.7 percentage of participants Interval 73.1 to 84.9	71.4 percentage of participants Interval 64.3 to 77.3
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 84 Months	68.5 percentage of participants Interval 60.0 to 75.5	79.7 percentage of participants Interval 73.1 to 84.9	67.2 percentage of participants Interval 59.9 to 73.5
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 96 Months	66.5 percentage of participants Interval 57.9 to 73.8	79.1 percentage of participants Interval 72.3 to 84.3	65.9 percentage of participants Interval 58.6 to 72.3
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 108 Months	63.3 percentage of participants Interval 54.3 to 71.0	78.4 percentage of participants Interval 71.6 to 83.7	65.3 percentage of participants Interval 57.9 to 71.7
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 120 Months	61 percentage of participants Interval 51.8 to 69.0	77 percentage of participants Interval 70.0 to 82.5	63.8 percentage of participants Interval 56.3 to 70.4
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 132 Months	59.7 percentage of participants Interval 50.4 to 67.9	75.4 percentage of participants Interval 68.2 to 81.2	62.3 percentage of participants Interval 54.6 to 69.0
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 144 Months	57 percentage of participants Interval 47.2 to 65.5	73.8 percentage of participants Interval 66.4 to 79.8	60.8 percentage of participants Interval 53.0 to 67.6
Percentage of Participants Alive Over Time Based on Kaplan-Meier Estimates 156 Months	55.5 percentage of participants Interval 45.6 to 64.3	70.1 percentage of participants Interval 62.1 to 76.7	60.8 percentage of participants Interval 53.0 to 67.6

Adverse Events

All Participants With Chronic Myeloid Leukemia

Serious events: 13 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants With Chronic Myeloid Leukemia n=532 participants at risk 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).
Injury, poisoning and procedural complications Hip fracture	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Injury, poisoning and procedural complications Fall	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Injury, poisoning and procedural complications Head injury	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Adenocarcinoma	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Cardiac disorders Atrial fibrillation	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Blood and lymphatic system disorders Febrile neutropenia	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Respiratory, thoracic and mediastinal disorders Asthma	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
General disorders Generalised oedema	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Gastrointestinal disorders Anal fistula	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Gastrointestinal disorders Inflammatory bowel disease	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Gastrointestinal disorders Gastrointestinal pain	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Psychiatric disorders Mental disorder	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Renal and urinary disorders Pollakiuria	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.
Infections and infestations Sepsis	0.19% 1/532 • Up to approximately 14 years Safety population included all participants who received at least 1 dose of study drug. Serious adverse events were not collected separately for each disease group (hematologic failure, cytogenetic failure and interferon-alpha intolerant) of participants. All the participants were properly combined for analysis, regardless of the disease groups. Other non-serious adverse events were not collected during the extension phase within the clinical database.

Other adverse events

Adverse event data not reported

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER