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To determine the long term safety and tolerability of dasatinib exposure in subjects previously treated in CA180-002.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dasatinib | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dasatinib | Drug | Tablets, Oral, The dosing ranges from 50mg to a total of 240mg daily with the following 3 schedules:
Once Daily (QD) or Twice Daily (BID) dosing, Subjects will be treated until progression of disease despite escalation/reductions of dose to the level deemed safe by available data, until intolerable/unacceptable toxicity or until subject withdrawal from the study or discontinuation of the study |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation. | AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled. | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
| Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs. | Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy. | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
| Number of Participants With Grade 3-4 Hematology Abnormalities | Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Platelets: Grade 3: 25.0 - <50.0*10^9/L, Grade 4: <25.0*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - <2.0*10^9/L, Grade 4: <1.0*10^9/L. | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
| Number of Participants With Grade 3-4 Serum Chemistry Abnormalities |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Complete Hematologic Response (CHR) | CHR should meet all of the following criteria: WBC <= Institutional ULN; ANC >= 1000/mm^3 ; Platelets < 450 000/mm^3 , no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; basophils in peripheral blood < 20% and no extramedullary involvement (including no hepatomegaly or splenomegaly). CHR can begin only 14 days after the start of treatment. |
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This study enrolled participants with Philadelphia chromosome positive (Ph+)chronic myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who had demonstrated hematologic resistance or intolerance to imatinib mesylate (Gleevec) and had experienced clinical benefit (in Investigator's opinion) on protocol CA180002.
Inclusion Criteria:
Exclusion Criteria:
Medical History and Concurrent Diseases
A serious uncontrolled medical disorder or active infection which would impair the ability of the patient to receive protocol therapy;
Uncontrolled angina within 3 months
Diagnosed or suspected congenital long QT syndrome
Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
Prolonged corrected QT(QTc) interval on pre-entry electrocardiogram (> 450 msec)
Uncontrolled hypertension
Dementia or altered mental status that would prohibit the understanding or rendering of informed consent;
History of significant bleeding disorder unrelated to CML, including:
Physical and Laboratory Test Findings
Prohibited Therapies and/or Medications
Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
Medications that inhibit platelet function and any non-steroidal anti-inflammatory drug) or anticoagulants are prohibited unless a previous exception on CA180-002 was granted by the medical monitor. Subjects taking anagrelide for thrombocytosis due to CML are eligible for this protocol
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry | Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| FG001 | CML: BID Dosing at Study Entry | Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| FG002 | Accelerated Phase CML: BID Dosing at Study Entry | Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| FG003 | Myeloid Blast Phase CML: BID Dosing at Study Entry | Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry | Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation. | AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled. | All treated participants. | Posted | Number | participants | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
|
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The SAEs listed here differ from those present in the Outcome Measures. This is because the Outcome Measures present on-treatment SAEs and this section presents all SAEs. In addition, the AEs presented here differ from those in the Outcome Measures. This is because the AEs presented here do not include SAEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants With Accelerated Phase CML | Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg ). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ARRHYTHMIA | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| EYE PRURITUS | Eye disorders | MedDRA 11.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| BMS Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069439 | Dasatinib |
| D019061 | src-Family Kinases |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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|
|
Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 * ULN (upper limit of normal), Grade 4: >20.0 * ULN; Calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; Bilirubin: Grade 3: >3-10 * ULN, Grade 4: >10 * ULN; Creatinine: Grade 3: >3.0-6.0 * ULN, Grade 4: >6.0 * ULN; Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-<0.8 or >2.46-6.6mEq/L, Grade 4: <0.6 or >6.6mEq/L. |
| From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
| Number of Participants With Dose Interruptions and Dose Reductions | Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times. | From start of study to final assessment (up to 32.2 months). |
| Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Median Number of Months of CHR (Kaplan Meier Method) | CHR: WBC<=ULN (range: 9.29-12.5*10^3 c\uL); ANC >=1000/mm^3;Platelets <450000/mm^3,no blasts/promyelocytes in peripheral blood; <5% myelocytes+metamyelocytes in peripheral blood; basophils in peripheral blood <20% & no extramedullary involvement. Duration computed for chronic phase participants, measured in months from first day CHR criteria met, provided they are confirmed 4 weeks later, until progression of disease, treatment discontinuation due to progressive disease or death. Participants who neither discontinue due to progression, nor progress nor die censored on date of last assessment. | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Number of Participants With Major Cytogenetic Response (MCyR) | Cytogenetic responses are based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. MCyR is defined as number of participants with Complete Cytogenetic Response (CCyR): 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow. | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Median Number of Months of Major Cytogenetic Response (MCyR) | MCyR: 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.The duration of MCyR was computed for chronic phase participants whose best response is either CCyR or PCyR. It was measured in months from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the date of progression or death. Participants who neither progress nor die are censored on the date of their last cytogenetic assessment. | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Number of Participants With Best Cytogenetic Response | Cytogenetic responses are based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. CCyR: 0% Ph+ cells in metaphase in bone marrow, PCyR: >0% to 35% Ph+ cells in metaphase in bone marrow, Minor CyR: >35% to 65% Ph+ cells in metaphase in bone marrow, Minimal CyR: >65% to 95% Ph+ cells in metaphase in bone marrow and No CyR: >95% to 100% Ph+ cells in metaphase in bone marrow. | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method) | Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used. | Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Median Number of Months of Overall Survival (OS) (Kaplan Meier Method) | Overall survival was defined as the median number of months from baseline to death from any cause. | Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
| Lost to Follow-up |
|
| Adverse Event |
|
| Participant's request |
|
| Administrative reason |
|
| Deterioration without progression |
|
| Disease progression/relapse |
|
| Study closure |
|
| No response |
|
| BG001 | CML: BID Dosing at Study Entry | Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| BG002 | Accelerated Phase CML: BID Dosing at Study Entry | Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| BG003 | Myeloid Blast Phase CML: BID Dosing at Study Entry | Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) | The ECOG PS is used to assess disease severity, with 0 being the least severe score and 5 being the most severe score. A score of 0 is fully active; 1 is restricted physically strenuous activity; 2 is ambulatory but unable to work; 3 is capable of only limited self care; 4 is completely disabled; 5 is dead. | Number | participants |
|
Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| OG001 | CML: BID Dosing at Study Entry | Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| OG002 | Accelerated Phase CML: BID Dosing at Study Entry | Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
| OG003 | Myeloid Blast Phase CML: BID Dosing at Study Entry | Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. |
|
|
| Primary | Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs. | Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy. | All treated participants. | Posted | Number | participants | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Primary | Number of Participants With Grade 3-4 Hematology Abnormalities | Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Platelets: Grade 3: 25.0 - <50.0*10^9/L, Grade 4: <25.0*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - <2.0*10^9/L, Grade 4: <1.0*10^9/L. | All treated participants. | Posted | Number | participants | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Secondary | Number of Participants With Complete Hematologic Response (CHR) | CHR should meet all of the following criteria: WBC <= Institutional ULN; ANC >= 1000/mm^3 ; Platelets < 450 000/mm^3 , no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; basophils in peripheral blood < 20% and no extramedullary involvement (including no hepatomegaly or splenomegaly). CHR can begin only 14 days after the start of treatment. | All treated participants. Data was not analyzed and reported for the other two groups (Accelerated Phase CML and Myeloid Blast Phase CML) due to small sample sizes. | Posted | Number | participants | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Secondary | Median Number of Months of CHR (Kaplan Meier Method) | CHR: WBC<=ULN (range: 9.29-12.5*10^3 c\uL); ANC >=1000/mm^3;Platelets <450000/mm^3,no blasts/promyelocytes in peripheral blood; <5% myelocytes+metamyelocytes in peripheral blood; basophils in peripheral blood <20% & no extramedullary involvement. Duration computed for chronic phase participants, measured in months from first day CHR criteria met, provided they are confirmed 4 weeks later, until progression of disease, treatment discontinuation due to progressive disease or death. Participants who neither discontinue due to progression, nor progress nor die censored on date of last assessment. | All treated participants with CML (whether QD or BID dosing), who had CHR. Data were not analyzed and reported for the other two groups (Accelerated Phase CML and Myeloid Blast Phase CML) due to small sample sizes. | Posted | Median | 95% Confidence Interval | months | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Secondary | Number of Participants With Major Cytogenetic Response (MCyR) | Cytogenetic responses are based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. MCyR is defined as number of participants with Complete Cytogenetic Response (CCyR): 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow. | All treated participants with evaluable sample sizes. Data was not analyzed and reported for the Accelerated Phase CML and Myeloid Blast Phase CML groups due to small sample sizes, which would lead to response rate estimates that are not stable. | Posted | Number | participants | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
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| Primary | Number of Participants With Grade 3-4 Serum Chemistry Abnormalities | Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 * ULN (upper limit of normal), Grade 4: >20.0 * ULN; Calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; Bilirubin: Grade 3: >3-10 * ULN, Grade 4: >10 * ULN; Creatinine: Grade 3: >3.0-6.0 * ULN, Grade 4: >6.0 * ULN; Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-<0.8 or >2.46-6.6mEq/L, Grade 4: <0.6 or >6.6mEq/L. | All treated participants. | Posted | Number | participants | From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Secondary | Median Number of Months of Major Cytogenetic Response (MCyR) | MCyR: 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.The duration of MCyR was computed for chronic phase participants whose best response is either CCyR or PCyR. It was measured in months from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the date of progression or death. Participants who neither progress nor die are censored on the date of their last cytogenetic assessment. | All treated participants with CML (whether QD or BID dosing), who had MCyR (13 participants had MCyR in QD group and 9 in BID group). Data were not analyzed and reported for the other two groups (Accelerated Phase CML and Myeloid Blast Phase CML) due to small sample sizes. | Posted | Median | 95% Confidence Interval | months | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Primary | Number of Participants With Dose Interruptions and Dose Reductions | Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times. | All treated participants. | Posted | Number | participants | From start of study to final assessment (up to 32.2 months). |
|
|
|
| Secondary | Number of Participants With Best Cytogenetic Response | Cytogenetic responses are based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. CCyR: 0% Ph+ cells in metaphase in bone marrow, PCyR: >0% to 35% Ph+ cells in metaphase in bone marrow, Minor CyR: >35% to 65% Ph+ cells in metaphase in bone marrow, Minimal CyR: >65% to 95% Ph+ cells in metaphase in bone marrow and No CyR: >95% to 100% Ph+ cells in metaphase in bone marrow. | All treated participants with evaluable sample sizes. Data was not analyzed and reported for the Accelerated Phase CML and Myeloid Blast Phase CML groups due to small sample sizes, which would lead to response rate estimates that are not stable. | Posted | Number | participants | Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Secondary | Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method) | Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used. | All treated participants. | Posted | Median | 95% Confidence Interval | months | Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| Secondary | Median Number of Months of Overall Survival (OS) (Kaplan Meier Method) | Overall survival was defined as the median number of months from baseline to death from any cause. | All treated participants. | Posted | Median | 95% Confidence Interval | months | Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months. |
|
|
|
| 3 |
| 5 |
| 5 |
| 5 |
| EG001 | Participants With Chronic Myelogenous Leukemia(CML);QD Dosing | Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules: 5 days, on 2 days off; 6 days on, 1 day off; or continuous daily dosing. Participants were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to twice daily (BID) dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. | 10 | 22 | 21 | 22 |
| EG002 | Participants With CML; BID Dosing | Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg. Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. | 9 | 15 | 15 | 15 |
| EG003 | Participants With Myeloid Blast Phase CML | Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg ). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time. | 3 | 4 | 4 | 4 |
| MYOCARDIAL ISCHAEMIA | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| PERICARDIAL EFFUSION | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| CARDIO-RESPIRATORY ARREST | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| ACUTE MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| PERIPHERAL VASCULAR DISORDER | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
| MENTAL STATUS CHANGES | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| CEREBRAL HAEMORRHAGE | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| HAEMORRHAGE INTRACRANIAL | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| HAEMORRHOIDS | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| OESOPHAGITIS | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| ABDOMINAL HERNIA | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| GASTROINTESTINAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PNEUMONIA | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| UROSEPSIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| MENINGITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| APPENDICITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| ARTHRITIS BACTERIAL | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| CATHETER SITE CELLULITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| STAPHYLOCOCCAL INFECTION | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| HERPES ZOSTER DISSEMINATED | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| RENAL FAILURE ACUTE | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
|
| ANOREXIA | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
|
| HYPONATRAEMIA | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 11.1 | Systematic Assessment |
|
| JOINT INJURY | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
|
| TRANSFUSION-RELATED ACUTE LUNG INJURY | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
|
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| LUNG DISORDER | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| SLEEP APNOEA SYNDROME | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DEATH | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| HERNIA | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| METASTASIS | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
|
| BASAL CELL CARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
|
| LUNG NEOPLASM MALIGNANT | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
|
| BLAST CELL PROLIFERATION | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
|
| CHRONIC MYELOID LEUKAEMIA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
|
| TRANSITIONAL CELL CARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
|
| VISION BLURRED | Eye disorders | MedDRA 11.1 | Systematic Assessment |
|
| OCULAR HYPERAEMIA | Eye disorders | MedDRA 11.1 | Systematic Assessment |
|
| CARDIAC MURMUR | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| BLOOD CREATININE | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| WEIGHT DECREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| CHEST X-RAY ABNORMAL | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| BREATH SOUNDS ABNORMAL | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| ALANINE AMINOTRANSFERASE | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| BLOOD CHLORIDE INCREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| BLOOD URIC ACID INCREASED | Investigations | MedDRA 11.1 | Systematic Assessment |
|
| TACHYCARDIA | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| CARDIAC DISORDER | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| DILATATION ATRIAL | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| PERICARDIAL EFFUSION | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| DIASTOLIC DYSFUNCTION | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| CORONARY ARTERY DISEASE | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| VENTRICULAR TACHYCARDIA | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| RIGHT VENTRICULAR DYSFUNCTION | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
|
| PALLOR | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
| HAEMATOMA | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
| HYPERTENSION | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
| VASCULAR CALCIFICATION | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
| INTERMITTENT CLAUDICATION | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| HYPOAESTHESIA | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DRY MOUTH | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| ORAL PAIN | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| FLATULENCE | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| GINGIVITIS | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| STOMATITIS | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DIVERTICULUM | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| SWOLLEN TONGUE | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| RECTAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| STOMACH DISCOMFORT | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| SALIVARY GLAND CALCULUS | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| GASTROINTESTINAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| VERTIGO | Ear and labyrinth disorders | MedDRA 11.1 | Systematic Assessment |
|
| CYSTITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| MASTITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| PNEUMONIA | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| SINUSITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| BRONCHITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| HEPATITIS B | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| ORAL HERPES | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| FOLLICULITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| LYME DISEASE | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| LOBAR PNEUMONIA | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| NASOPHARYNGITIS | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| VIRAL INFECTION | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| URINARY TRACT INFECTION ENTEROCOCCAL | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
|
| NOCTURIA | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
|
| HAEMATURIA | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
|
| POLLAKIURIA | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
|
| ANOREXIA | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 11.1 | Systematic Assessment |
|
| SPLENOMEGALY | Blood and lymphatic system disorders | MedDRA 11.1 | Systematic Assessment |
|
| ACNE | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| ECCHYMOSIS | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| SKIN ULCER | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| SKIN LESION | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| NIGHT SWEATS | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| HYPERHIDROSIS | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| VAGINAL HAEMORRHAGE | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
|
| BENIGN PROSTATIC HYPERPLASIA | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
|
| CONTUSION | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
|
| JOINT INJURY | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| BONE PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| SPONDYLITIS | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| OSTEOPOROSIS | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| ASTHMA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| HYPOXIA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| EPISTAXIS | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| ATELECTASIS | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| BRONCHOSPASM | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PLEURITIC PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PULMONARY OEDEMA | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| SINUS CONGESTION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| RHINITIS ALLERGIC | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| OROPHARYNGEAL PAIN | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| DYSPNOEA EXERTIONAL | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PULMONARY HYPERTENSION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| PARANASAL SINUS HYPERSECRETION | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
|
| MASS | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| POLYP | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| CHILLS | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| PYREXIA | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| ASTHENIA | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| CALCINOSIS | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| CHEST PAIN | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| CHEST DISCOMFORT | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA 11.1 | Systematic Assessment |
|
| INFLUENZA LIKE ILLNESS | General disorders | MedDRA 11.1 | Systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D011505 | Protein-Tyrosine Kinases |
| D011494 | Protein Kinases |
| D017853 | Phosphotransferases (Alcohol Group Acceptor) |
| D010770 | Phosphotransferases |
| D014166 | Transferases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D047908 | Intracellular Signaling Peptides and Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| Drug-related SAEs |
|
| ANC |
|
| Platelet Count |
|
| Hemoglobin |
|
| High ALT |
|
| High Total Bilirubin |
|
| Low Calcium |
|
| Low Magnesium |
|
| High Serum Creatinine |
|
| Dose reductions |
|
| Minor (36-65%) |
|
| Minimal (66-95%) |
|
| No response |
|
| Unable to determine |
|