A Phase 2 interventional study of STI571 in Leukemia, Myelogenous, Chronic, BCR-ABL Positive, sponsored by Novartis Pharmaceuticals. Completed at 28 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-22.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
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.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 532 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participants included in the study were:
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.
Exclusion Criteria:
Participants excluded from the study were:
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).
Drug: STI571
STI571 oral capsules or tablets.
Also known as: Imatinib Mesylate
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
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
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
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
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
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
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
| Milestone | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Started | 152 | 188 | 192 |
| Completed | 12 | 47 | 22 |
| Not completed | 140 | 141 | 170 |
| Withdrew: Adverse event (non-fatal) | 6 | 5 | 19 |
| Withdrew: Abnormal laboratory value (s) | 4 | 2 | 3 |
| Withdrew: Abnormal procedure | 1 | 0 | 0 |
| Withdrew: Unsatisfactory therapeutic effect | 57 | 43 | 52 |
| Withdrew: No longer requires study drug (bone marrow transplant) | 2 | 4 | 2 |
| Withdrew: Protocol violation | 2 | 2 | 3 |
| Withdrew: Participant withdrew consent | 12 | 21 | 15 |
| Withdrew: Lost to follow-up | 5 | 2 | 3 |
| Withdrew: Administrative problems | 4 | 7 | 6 |
| Withdrew: Adverse event (serious fatal) | 6 | 8 | 9 |
| Withdrew: Not specified (no data collected after cut-off) | 41 | 47 | 58 |
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.
| percentage of participants | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Complete Cytogenetic Response | 29.6 (22.5 to 37.5) | 37.2 (30.3 to 44.6) | 45.8 (38.6 to 53.2) |
| Major Cytogenetic Response | 45.4 (37.3 to 53.7) | 63.8 (56.5 to 70.7) | 65.6 (58.4 to 72.3) |
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.
| percentage of participants | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Percentage of Participants With Complete Hematologic Response to STI571 | 94.1 (89.1 to 97.3) | 97.9 (94.6 to 99.4) | 91.7 (86.8 to 95.2) |
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.
| months | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Duration of Complete Hematologic Response to STI571 | 19.3672 ± 0.6383 | 23.9389 ± 0.506 | 24.6818 ± 0.6507 |
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.
| months | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Time to Complete Hematologic Response to STI571 | 1.64 (0.6 to 2.8) | 0.72 (0.3 to 2.8) | 0.72 (0.3 to 2.8) |
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.
| Participants | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Abdominal Discomfort Grade 3 | 0 | 0 | 0 |
| Abdominal Discomfort Grade 4 | 0 | 0 | 0 |
| Anorexia Grade 3 | 0 | 0 | 0 |
| Anorexia Grade 4 | 0 | 0 | 0 |
| Arthralgia Grade 3 | 0 | 0 | 1 |
| Arthralgia Grade 4 | 0 | 0 | 0 |
| Bone Pain Grade 3 | 0 | 1 | 0 |
| Bone Pain Grade 4 | 0 | 0 | 0 |
| Fatigue Grade 3 | 1 | 0 | 0 |
| Fatigue Grade 4 | 0 | 0 | 0 |
| Fever Grade 3 | 0 | 0 | 0 |
| Fever Grade 4 | 0 | 0 | 0 |
| Night Sweats Grade 3 | 0 | 0 | 0 |
| Night Sweats Grade 4 | 0 | 0 | 0 |
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.
| Participants | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| Grade 3 | 1 | 0 | 0 |
| Grade 4 | 0 | 0 | 0 |
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.
| percentage of participants | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance |
|---|---|---|---|
| 12 Months | 94.7 (89.8 to 97.3) | 98.9 (95.8 to 99.7) | 97.4 (93.9 to 98.9) |
| 24 Months | 88.1 (81.8 to 92.3) | 93.6 (89 to 96.3) | 89.5 (84.3 to 93.1) |
| 36 Months | 84 (77.1 to 89) | 91.5 (86.5 to 94.7) | 83.8 (77.7 to 88.3) |
| 48 Months | 78.4 (70.9 to 84.2) | 87.1 (81.4 to 91.2) | 76.3 (69.6 to 81.7) |
| 60 Months | 73.3 (65.2 to 79.7) | 83.8 (77.6 to 88.4) | 73.6 (66.7 to 79.3) |
| 72 Months | 70.1 (61.9 to 76.9) | 79.7 (73.1 to 84.9) | 71.4 (64.3 to 77.3) |
| 84 Months | 68.5 (60 to 75.5) | 79.7 (73.1 to 84.9) | 67.2 (59.9 to 73.5) |
| 96 Months | 66.5 (57.9 to 73.8) | 79.1 (72.3 to 84.3) | 65.9 (58.6 to 72.3) |
| 108 Months | 63.3 (54.3 to 71) | 78.4 (71.6 to 83.7) | 65.3 (57.9 to 71.7) |
| 120 Months | 61 (51.8 to 69) | 77 (70 to 82.5) | 63.8 (56.3 to 70.4) |
| 132 Months | 59.7 (50.4 to 67.9) | 75.4 (68.2 to 81.2) | 62.3 (54.6 to 69) |
| 144 Months | 57 (47.2 to 65.5) | 73.8 (66.4 to 79.8) | 60.8 (53 to 67.6) |
| 156 Months | 55.5 (45.6 to 64.3) | 70.1 (62.1 to 76.7) | 60.8 (53 to 67.6) |
Collected over Up to approximately 14 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| All Participants With Chronic Myeloid Leukemia | — | 13/532 (2.4%) | — |
| Event | All Participants With Chronic Myeloid Leukemia |
|---|---|
| Hip fractureInjury, poisoning and procedural complications | 1/532 |
| FallInjury, poisoning and procedural complications | 1/532 |
| Head injuryInjury, poisoning and procedural complications | 1/532 |
| SarcomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/532 |
| Prostate AdenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/532 |
| Atrial fibrillationCardiac disorders | 1/532 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/532 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 1/532 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 1/532 |
| Generalised oedemaGeneral disorders | 1/532 |
Intent-to-treat (ITT) population included all enrolled participants.
| Age, Continuous(years) | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance | Total |
|---|---|---|---|---|
| Median | 55.5 (18 to 79) | 53.0 (23 to 77) | 59.0 (20 to 90) | 57.0 (18 to 90) |
| Age, Customized(Participants) | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance | Total |
|---|---|---|---|---|
| Less than (<) 50 years | 57 | 64 | 47 | 168 |
| >= 50 to <= 60 years | 38 | 65 | 50 | 153 |
| >= 60 to <= 70 years | 47 | 44 | 68 | 159 |
| >= 70 years | 10 | 15 | 27 | 52 |
| Sex: Female, Male(Participants) | Hematologic Failure | Cytogenetic Failure | Interferon-alpha Intolerance | Total |
|---|---|---|---|---|
| Female | 50 | 77 | 94 | 221 |
| Male | 102 | 111 | 98 | 311 |
This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Novartis Pharmaceuticals