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Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses (OPTIC)

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ClinicalTrials.gov Identifier: NCT02467270
Recruitment Status : Active, not recruiting
First Posted : June 10, 2015
Results First Posted : June 14, 2021
Last Update Posted : February 6, 2024
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Myeloid Leukemia, Chronic, Chronic Phase
Intervention Drug: Ponatinib
Enrollment 283
Recruitment Details Participants took part in the study at 61 investigative sites in the Argentina, Austria, Chile, Denmark, France, United Kingdom, Hong Kong, Italy, Japan, Poland, Russia, Singapore, Korea, Republic of, Spain, Sweden, Taiwan, Province Of China, and United States from 30 June 2015 and up to data cut-off: 31 May 2020. The study is ongoing.
Pre-assignment Details Participants with diagnosis of chronic phase-chronic myelogenous leukemia (CP-CML) who received at least 2 prior tyrosine kinase inhibitor (TKI) therapies were enrolled in 1:1:1 ratio in 3 cohorts: ponatinib: 45 mg (Cohort A); 30 mg (Cohort B); or 15 mg (Cohort C). Participants who started at 45/30 mg received mandatory dose reduction of their daily dose to 15 mg upon achievement of ≤1% breakpoint cluster region-Abelson 1 transcript level as measured by International Scale (BCR-ABL1IS).
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily. Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily. Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Period Title: Overall Study
Started 94 95 94
Treated (Safety Population) [1] 94 94 94
Completed 0 0 0
Not Completed 94 95 94
Reason Not Completed
Participants Never Treated             0             1             0
Ongoing             50             41             43
Adverse Event             16             15             14
Progressive Disease             7             7             4
Death             2             0             2
Lack of Efficacy             12             18             23
Non-compliance With Study Drug             0             2             1
Lost to Follow-up             2             1             0
Pregnancy             0             1             0
Physician Decision             0             4             1
Withdrawal by Subject             4             3             5
Reason not Specified             1             2             1
[1]
Included all participants who received at least one dose of study drug.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg Total
Hide Arm/Group Description Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily. Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily. Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle. Total of all reporting groups
Overall Number of Baseline Participants 94 94 94 282
Hide Baseline Analysis Population Description
Safety Population included all participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 94 participants 94 participants 94 participants 282 participants
47.7  (14.77) 48.5  (12.90) 48.8  (12.71) 48.3  (13.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants 94 participants 94 participants 282 participants
Female
44
  46.8%
56
  59.6%
41
  43.6%
141
  50.0%
Male
50
  53.2%
38
  40.4%
53
  56.4%
141
  50.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants 94 participants 94 participants 282 participants
Hispanic or Latino
22
  23.4%
26
  27.7%
20
  21.3%
68
  24.1%
Not Hispanic or Latino
70
  74.5%
67
  71.3%
72
  76.6%
209
  74.1%
Unknown or Not Reported
2
   2.1%
1
   1.1%
2
   2.1%
5
   1.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 94 participants 94 participants 94 participants 282 participants
Asian
16
  17.0%
12
  12.8%
15
  16.0%
43
  15.2%
Black or African American
1
   1.1%
2
   2.1%
3
   3.2%
6
   2.1%
White
73
  77.7%
77
  81.9%
72
  76.6%
222
  78.7%
Unknown
0
   0.0%
1
   1.1%
3
   3.2%
4
   1.4%
Other
2
   2.1%
1
   1.1%
0
   0.0%
3
   1.1%
Missing
2
   2.1%
1
   1.1%
1
   1.1%
4
   1.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Argentina Number Analyzed 94 participants 94 participants 94 participants 282 participants
15
  16.0%
16
  17.0%
7
   7.4%
38
  13.5%
Austria Number Analyzed 94 participants 94 participants 94 participants 282 participants
0
   0.0%
0
   0.0%
2
   2.1%
2
   0.7%
Chile Number Analyzed 94 participants 94 participants 94 participants 282 participants
7
   7.4%
9
   9.6%
9
   9.6%
25
   8.9%
Denmark Number Analyzed 94 participants 94 participants 94 participants 282 participants
0
   0.0%
0
   0.0%
1
   1.1%
1
   0.4%
France Number Analyzed 94 participants 94 participants 94 participants 282 participants
2
   2.1%
1
   1.1%
2
   2.1%
5
   1.8%
United Kingdom Number Analyzed 94 participants 94 participants 94 participants 282 participants
1
   1.1%
4
   4.3%
7
   7.4%
12
   4.3%
Hong Kong Number Analyzed 94 participants 94 participants 94 participants 282 participants
1
   1.1%
3
   3.2%
2
   2.1%
6
   2.1%
Italy Number Analyzed 94 participants 94 participants 94 participants 282 participants
0
   0.0%
3
   3.2%
0
   0.0%
3
   1.1%
Japan Number Analyzed 94 participants 94 participants 94 participants 282 participants
5
   5.3%
2
   2.1%
4
   4.3%
11
   3.9%
Poland Number Analyzed 94 participants 94 participants 94 participants 282 participants
4
   4.3%
6
   6.4%
5
   5.3%
15
   5.3%
Russia Number Analyzed 94 participants 94 participants 94 participants 282 participants
38
  40.4%
31
  33.0%
38
  40.4%
107
  37.9%
Singapore Number Analyzed 94 participants 94 participants 94 participants 282 participants
4
   4.3%
3
   3.2%
2
   2.1%
9
   3.2%
Korea, Republic Of Number Analyzed 94 participants 94 participants 94 participants 282 participants
0
   0.0%
3
   3.2%
2
   2.1%
5
   1.8%
Spain Number Analyzed 94 participants 94 participants 94 participants 282 participants
2
   2.1%
1
   1.1%
2
   2.1%
5
   1.8%
Sweden Number Analyzed 94 participants 94 participants 94 participants 282 participants
1
   1.1%
2
   2.1%
2
   2.1%
5
   1.8%
Taiwan, Province Of China Number Analyzed 94 participants 94 participants 94 participants 282 participants
4
   4.3%
1
   1.1%
2
   2.1%
7
   2.5%
United States Number Analyzed 94 participants 94 participants 94 participants 282 participants
10
  10.6%
9
   9.6%
7
   7.4%
26
   9.2%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 94 participants 94 participants 94 participants 282 participants
78.14  (20.841) 77.56  (18.375) 76.71  (17.434) 77.47  (18.879)
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Meter
Number Analyzed 94 participants 91 participants 92 participants 277 participants
1.68  (0.104) 1.68  (0.098) 1.68  (0.090) 1.68  (0.097)
[1]
Measure Analysis Population Description: Number analyzed is the number of participants with data available for height at Baseline.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Score= 0 Number Analyzed 94 participants 94 participants 94 participants 282 participants
74
  78.7%
73
  77.7%
72
  76.6%
219
  77.7%
Score= 1 Number Analyzed 94 participants 94 participants 94 participants 282 participants
19
  20.2%
20
  21.3%
22
  23.4%
61
  21.6%
Score= 2 Number Analyzed 94 participants 94 participants 94 participants 282 participants
1
   1.1%
1
   1.1%
0
   0.0%
2
   0.7%
[1]
Measure Description: ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity). Only categories with data are reported.
1.Primary Outcome
Title Percentage of Participants With Molecular Response (MR2: <=1% Breakpoint Cluster Region-Abelson Transcript Level) as Measured by the International Scale (BCR-ABL1IS) at Month 12
Hide Description MR2 is defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL <=1% Breakpoint Cluster Region-Abelson Transcript Level as Measured by the International Scale (BCR-ABL1IS), equivalent to a 2-log reduction in transcript.
Time Frame 12 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 93 93 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
44.1
(33.8 to 54.8)
29.0
(20.1 to 39.4)
23.1
(14.9 to 33.1)
2.Secondary Outcome
Title Percentage of Participants With Major Molecular Response (MMR/MR3)
Hide Description MMR/MR3 is defined as a ratio of reverse transcribed transcript of BCR-ABL to ABL ≤0.1% on the international scale (equivalent to a 3-log reduction in transcript).
Time Frame 12 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 93 93 91
Measure Type: Number
Unit of Measure: percentage of participants
17.2 20.4 16.5
3.Secondary Outcome
Title Percentage of Participants With Major Cytogenetic Response (MCyR)
Hide Description MCyR is defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: 0% Ph + metaphases; PCyR: >0 to 35% Ph + metaphases.
Time Frame 12 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Cytogenetic Population included all participants who were randomized and had a cytogenetic assessment at Baseline with ≥20 metaphases examined, regardless of whether they received the assigned study drug. Overall number analyzed are participants with data available for analysis.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 91 90 89
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
48.4
(37.7 to 59.1)
27.8
(18.9 to 38.2)
43.8
(33.3 to 54.7)
4.Secondary Outcome
Title Duration of Major Molecular Response (MMR/MR3)
Hide Description Duration of MMR/MR3 is defined as the interval between the first assessment at which the criteria for <=0.1% MMR are met until the earliest date at which loss of <=0.1% MMR occurs, or the criteria for progression are met. Progression to accelerated phase (AP) is defined as: >= 15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets per liter (/L) in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to blast Phase (BP) is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Time Frame Baseline up to approximately 8 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Percentage of Participants With Adjusted Incidence Rates for Treatment Emergent Arterial Occlusive Events (AOEs), Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)
Hide Description Percentage of participants with adjusted incidence rates who developed AOEs and VTEs were categorized according to arterial occlusive events and venous thrombotic events. AE is any untoward medical occurrence in participant administered medicinal investigational drug. Untoward medical occurrence does not necessarily have to have causal relationship with treatment. SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is congenital anomaly/birth defect/is medically important event that may not be immediately life-threatening/result in death or hospitalization, but may jeopardize participant/may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Time Frame From first dose up to 30 days after last dose of the study drug up to data cut-off date: 31 May 2020 (Up to approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study drug.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 94 94 94
Measure Type: Number
Unit of Measure: percentage of participants
AOEs 9.6 5.3 3.2
VTEs 1.1 0 0
AEs 100.0 93.6 94.7
SAEs 34.0 25.5 33.0
6.Secondary Outcome
Title Percentage of Participants With Complete Cytogenetic Response (CCyR)
Hide Description Cytogenetic response is defined as the percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. CCyR is defined as 0% Ph+ metaphases.
Time Frame Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Cytogenetic Population included all participants who were randomized and had a cytogenetic assessment at Baseline with ≥20 metaphases examined, regardless of whether they received the assigned study drug. Overall number analyzed are participants with data available for analysis.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 91 90 89
Measure Type: Number
Unit of Measure: percentage of participants
34.1 17.8 29.2
7.Secondary Outcome
Title Percentage of Participants With Molecular Response 4 (MR4) and Molecular Response (MR4.5)
Hide Description MR4 is defined as <=0.01% BCR-ABL1IS. MR 4.5 is defined as <=0.0032% BCR-ALB1IS.
Time Frame Up to approximately 8 years
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Percentage of Participants With Molecular Response 1 (MR1)
Hide Description MR1 is defined as percentage of participants achieving a ratio of <=10% Breakpoint Cluster Region-abelson (BCR-ABL1) transcripts on the international scale. MR1 is molecular response with 1-log reduction in transcript.
Time Frame 3 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 93 93 91
Measure Type: Number
Unit of Measure: percentage of participants
52.7 44.1 42.9
9.Secondary Outcome
Title Percentage of Participants With Complete Hematologic Response (CHR)
Hide Description CHR is defined as achieving all of the following measurements: white blood cells (WBC) <= institutional upper limit of normal (ULN), platelets <450,000 per cubic millimeter (/mm^3), no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, and no extramedullary involvement (including no hepatomegaly or splenomegaly).
Time Frame 3 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included in the analysis.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 94 95 94
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
87.2
(78.8 to 93.2)
81.1
(71.7 to 88.4)
81.9
(72.6 to 89.1)
10.Secondary Outcome
Title Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
Hide Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame Up to data cut-off: 31 May 2020 (Approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population included all participants who received at least 1 dose of study drug.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 94 94 94
Measure Type: Number
Unit of Measure: percentage of participants
TEAEs Leading to Treatment Discontinuation 19.1 16.0 13.8
TEAEs Leading to Dose Reduction 45.7 35.1 31.9
TEAEs Leading to Dose Interruption 71.3 61.7 58.5
11.Secondary Outcome
Title Kaplan-Meier Estimate of Duration of Response (DOR) of <=1% BCR-ABL1 IS (MR2) at Months 12 and 24
Hide Description DOR (≤1% BCR-ABL1IS) is defined as interval between first assessment at which criteria for ≤1% BCR-ABL1IS are met until earliest date at which loss of ≤1% BCR-ABL1IS occurs, or criteria for progression accelerated phase (AP) or blast Phase (BP) of chronic myeloid leukemia (CML) are met. Loss of ≤1% BCR-ABL1IS is an increase to >1% of BCR-ABL1IS. Progression to AP: ≥15% and <30% blasts in peripheral blood or bone marrow or ≥20% basophils in peripheral blood or bone marrow or ≥30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets per liter in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: ≥30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.
Time Frame 12 and 24 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Data is reported for responders.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 52 35 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 12
79.13
(64.5 to 88.3)
79.20
(61.2 to 89.5)
90.10
(72.4 to 96.7)
Month 24
73.17
(57.0 to 84.1)
75.60
(56.9 to 87.0)
90.10
(72.4 to 96.7)
12.Secondary Outcome
Title Kaplan-Meier Estimate of Duration of Response (DOR) of Major Molecular Response (MMR/MR3)
Hide Description Duration of MMR/MR3 is defined as interval between first assessment at which criteria for MMR are met until earliest date at which loss of MMR occurs, or criteria for progression (progression to AP or BP of CML) are met. Participants remaining in MMR will be censored at last date at which criteria for MMR are met. Loss of MMR is an increase to >0.1% of BCR-ABL1IS. Progression to AP: >= 15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts+promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. Kaplan-Meier method was used for analysis of percentage of participants who achieved DOR of 12 and 24 months.
Time Frame 12 and 24 months after the first dose of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Data is reported for responders.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 32 24 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 12
88.97
(69.5 to 96.3)
93.33
(61.3 to 99.0)
94.74
(68.1 to 99.2)
Month 24
88.97
(69.5 to 96.3)
84.00
(48.7 to 95.9)
94.74
(68.1 to 99.2)
13.Secondary Outcome
Title Duration of Response in Responders
Hide Description Duration of response in "responders" is defined as any participants who achieved ≤1% BCR-ABL1IS at any time during the study. Responders are defined as those participants who meet all of the following: are randomized and treated, respond at 12 months after the initiation of study treatment, and undergo baseline polymerase chain reaction (PCR) assessment.
Time Frame Baseline up to data cut-off: 31 May 2020 (Approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Data is reported for responders.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 52 35 33
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(26.9 to NA)
NA [2] 
(27.3 to NA)
NA [3] 
(NA to NA)
[1]
Median and upper limit of 95% confidence interval (CI) was not estimable as participants were censored.
[2]
Median and upper limit of 95% CI was not estimable as participants were censored.
[3]
Median, upper limit and lower limit of 95% CI was not estimable as participants were censored.
14.Secondary Outcome
Title Time to Response
Hide Description Time to response was defined as the time interval from the date of the first dose of the study drug until the initial observation of CR or PR for participants with confirmed CR/PR. CR for target lesion: disappearance of all extranodal lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. CR for non-target lesion: Disappearance of all extranodal non-target lesions, all lymph nodes must be non-pathological in size (<10mm short axis) and norrmalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the Baseline sum diameters.
Time Frame Baseline up to data cut-off: 31 May 2020 (Approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population included all participants who were randomized and for whom BCR-ABL1IS could be measured (ie, participants who had the b2a2/b3a2 transcript type), regardless of whether they received the assigned study drug. Data is reported for the responders.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 52 35 33
Median (95% Confidence Interval)
Unit of Measure: months
6.00
(3.1 to 6.0)
3.04
(3.0 to 6.0)
6.04
(3.0 to 9.1)
15.Secondary Outcome
Title Percentage of Participants With Progression to Accelerated Phase (AP)-Chronic Myeloid Leukemia (CML) or Blast Phase (BP)-CML
Hide Description Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Time Frame From first dose date of study treatment up to data cut-off: 31 May 2020 (Approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included in the analysis.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 94 95 94
Measure Type: Number
Unit of Measure: percentage of participants
Progressed to AP-CML 10.6 9.5 11.7
Progressed to BP-CML 3.2 1.1 1.1
16.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS is defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression are met (progression to the AP or BP of CML), or death due to any cause, censored at the last response assessment. Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.
Time Frame Up to data cut-off: 31 May 2020 (Up to approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included in the analysis.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 94 95 94
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [2] 
(35.6 to NA)
45.64 [3] 
(38.7 to NA)
[1]
Median, Lower limit and Upper limit of 95% confidence interval was not estimable due to low number of participants with event.
[2]
Median and Upper limit of 95% confidence interval was not estimable due to low number of participants with event.
[3]
Upper limit of 95% confidence interval was not estimable due to low number of participants with event.
17.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the interval between the first does of study treatment and death due to any cause, censored at the last contact date when the participant was alive.
Time Frame Up to data cut-off: 31 May 2020 (Up to approximately 5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants were included in the analysis.
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description:
Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.
Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
Overall Number of Participants Analyzed 94 95 94
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median, Lower limit and Upper limit of 95% confidence interval was not estimable due to low number of participants with event.
Time Frame From first dose up to 30 days after last dose of the study drug up to data cut-off: 31 May 2020 (Up to approximately 5 years)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. All cause-mortality was collected for all randomized participants. Serious and other adverse events was collected for participants from Safety Population who received at least 1 dose of study drug.
 
Arm/Group Title Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Hide Arm/Group Description Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily. Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily. Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.
All-Cause Mortality
Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/94 (8.51%)   7/95 (7.37%)   8/94 (8.51%) 
Hide Serious Adverse Events
Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/94 (34.04%)   24/94 (25.53%)   31/94 (32.98%) 
Blood and lymphatic system disorders       
Thrombocytopenia † 1  5/94 (5.32%)  2/94 (2.13%)  5/94 (5.32%) 
Neutropenia † 1  2/94 (2.13%)  1/94 (1.06%)  3/94 (3.19%) 
Anaemia † 1  3/94 (3.19%)  0/94 (0.00%)  0/94 (0.00%) 
Febrile neutropenia † 1  1/94 (1.06%)  0/94 (0.00%)  2/94 (2.13%) 
Pancytopenia † 1  0/94 (0.00%)  1/94 (1.06%)  1/94 (1.06%) 
Bone marrow failure † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Splenomegaly † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Cardiac disorders       
Atrial fibrillation † 1  2/94 (2.13%)  2/94 (2.13%)  1/94 (1.06%) 
Acute coronary syndrome † 1  1/94 (1.06%)  1/94 (1.06%)  0/94 (0.00%) 
Acute myocardial infarction † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Atrial flutter † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Cardio-respiratory arrest † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Myocardial infarction † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Myocardial ischaemia † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Pericarditis † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Ventricular tachycardia † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Angina unstable † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Endocrine disorders       
Thyroiditis † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Eye disorders       
Age-related macular degeneration † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Gastrointestinal disorders       
Abdominal pain † 1  1/94 (1.06%)  0/94 (0.00%)  1/94 (1.06%) 
Abdominal pain upper † 1  2/94 (2.13%)  0/94 (0.00%)  0/94 (0.00%) 
Pancreatitis † 1  1/94 (1.06%)  1/94 (1.06%)  0/94 (0.00%) 
Pancreatitis acute † 1  1/94 (1.06%)  0/94 (0.00%)  1/94 (1.06%) 
Coeliac artery stenosis † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Gastritis † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Haematemesis † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Small intestinal haemorrhage † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Vomiting † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Mesenteric vascular Insufficiency † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
General disorders       
Pyrexia † 1  4/94 (4.26%)  0/94 (0.00%)  1/94 (1.06%) 
Sudden death † 1  2/94 (2.13%)  0/94 (0.00%)  0/94 (0.00%) 
Fatigue † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
General physical health deterioration † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Influenza like illness † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Hepatobiliary disorders       
Acute hepatic failure † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Cholecystitis † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Cholecystitis acute † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Cholelithiasis † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Hepatic function abnormal † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Hepatotoxicity † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Infections and infestations       
Pneumonia † 1  0/94 (0.00%)  1/94 (1.06%)  3/94 (3.19%) 
Cellulitis † 1  0/94 (0.00%)  0/94 (0.00%)  2/94 (2.13%) 
Sepsis † 1  1/94 (1.06%)  1/94 (1.06%)  0/94 (0.00%) 
Gastroenteritis viral † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Infection † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Influenza † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Localised infection † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Meningitis † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Neutropenic sepsis † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Respiratory tract infection † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Urinary tract infection † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Appendicitis † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
COVID-19 pneumonia † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Tooth abscess † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Injury, poisoning and procedural complications       
Subdural haematoma † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Tibia fracture † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Investigations       
Lipase increased † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Metabolism and nutrition disorders       
Dehydration † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Tumour lysis syndrome † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Osteoarthritis † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenocarcinoma of colon † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Malignant melanoma † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Blast crisis in myelogenous leukaemia † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Nervous system disorders       
Dizziness † 1  0/94 (0.00%)  2/94 (2.13%)  0/94 (0.00%) 
Ischaemic stroke † 1  1/94 (1.06%)  1/94 (1.06%)  2/94 (2.13%) 
Cerebral haematoma † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Facial nerve disorder † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Headache † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Seizure † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Cerebrovascular accident † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Renal and urinary disorders       
Acute kidney injury † 1  0/94 (0.00%)  1/94 (1.06%)  1/94 (1.06%) 
Renal colic † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Reproductive system and breast disorders       
Metrorrhagia † 1  0/94 (0.00%)  1/94 (1.06%)  0/94 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea † 1  1/94 (1.06%)  1/94 (1.06%)  0/94 (0.00%) 
Skin and subcutaneous tissue disorders       
Erythema multiforme † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Rash erythematous † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Rash pruritic † 1  0/94 (0.00%)  0/94 (0.00%)  1/94 (1.06%) 
Vascular disorders       
Hypertension † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
Hypertensive crisis † 1  1/94 (1.06%)  0/94 (0.00%)  0/94 (0.00%) 
1
Term from vocabulary, MedDRA Version 22.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A: Ponatinib 45 mg Cohort B: Ponatinib 30 mg Cohort C: Ponatinib 15 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   92/94 (97.87%)   85/94 (90.43%)   86/94 (91.49%) 
Blood and lymphatic system disorders       
Thrombocytopenia † 1  40/94 (42.55%)  36/94 (38.30%)  35/94 (37.23%) 
Neutropenia † 1  28/94 (29.79%)  22/94 (23.40%)  23/94 (24.47%) 
Anaemia † 1  20/94 (21.28%)  17/94 (18.09%)  16/94 (17.02%) 
Leukopenia † 1  5/94 (5.32%)  4/94 (4.26%)  7/94 (7.45%) 
Gastrointestinal disorders       
Constipation † 1  10/94 (10.64%)  11/94 (11.70%)  14/94 (14.89%) 
Abdominal pain † 1  9/94 (9.57%)  8/94 (8.51%)  7/94 (7.45%) 
Abdominal pain upper † 1  8/94 (8.51%)  10/94 (10.64%)  3/94 (3.19%) 
Nausea † 1  7/94 (7.45%)  8/94 (8.51%)  8/94 (8.51%) 
Diarrhoea † 1  4/94 (4.26%)  4/94 (4.26%)  9/94 (9.57%) 
Vomiting † 1  4/94 (4.26%)  8/94 (8.51%)  5/94 (5.32%) 
Dyspepsia † 1  3/94 (3.19%)  5/94 (5.32%)  3/94 (3.19%) 
General disorders       
Fatigue † 1  7/94 (7.45%)  7/94 (7.45%)  4/94 (4.26%) 
Pyrexia † 1  14/94 (14.89%)  4/94 (4.26%)  9/94 (9.57%) 
Asthenia † 1  3/94 (3.19%)  5/94 (5.32%)  2/94 (2.13%) 
Non-cardiac chest pain † 1  1/94 (1.06%)  5/94 (5.32%)  2/94 (2.13%) 
Infections and infestations       
Folliculitis † 1  5/94 (5.32%)  0/94 (0.00%)  1/94 (1.06%) 
Upper respiratory tract infection † 1  7/94 (7.45%)  4/94 (4.26%)  6/94 (6.38%) 
Investigations       
Lipase increased † 1  19/94 (20.21%)  17/94 (18.09%)  12/94 (12.77%) 
Platelet count decreased † 1  11/94 (11.70%)  9/94 (9.57%)  10/94 (10.64%) 
Alanine aminotransferase increased † 1  21/94 (22.34%)  6/94 (6.38%)  16/94 (17.02%) 
Aspartate aminotransferase increased † 1  13/94 (13.83%)  3/94 (3.19%)  8/94 (8.51%) 
Blood alkaline phosphatase increased † 1  5/94 (5.32%)  3/94 (3.19%)  7/94 (7.45%) 
Blood cholesterol increased † 1  5/94 (5.32%)  4/94 (4.26%)  5/94 (5.32%) 
Amylase increased † 1  5/94 (5.32%)  3/94 (3.19%)  1/94 (1.06%) 
Blood triglycerides increased † 1  5/94 (5.32%)  1/94 (1.06%)  2/94 (2.13%) 
Metabolism and nutrition disorders       
Hypertriglyceridaemia † 1  14/94 (14.89%)  9/94 (9.57%)  9/94 (9.57%) 
Hypercholesterolaemia † 1  5/94 (5.32%)  5/94 (5.32%)  7/94 (7.45%) 
Hyperglycaemia † 1  5/94 (5.32%)  10/94 (10.64%)  8/94 (8.51%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  9/94 (9.57%)  20/94 (21.28%)  13/94 (13.83%) 
Myalgia † 1  7/94 (7.45%)  6/94 (6.38%)  10/94 (10.64%) 
Musculoskeletal pain † 1  5/94 (5.32%)  8/94 (8.51%)  3/94 (3.19%) 
Pain in extremity † 1  8/94 (8.51%)  9/94 (9.57%)  7/94 (7.45%) 
Back pain † 1  7/94 (7.45%)  9/94 (9.57%)  5/94 (5.32%) 
Nervous system disorders       
Headache † 1  16/94 (17.02%)  16/94 (17.02%)  18/94 (19.15%) 
Dizziness † 1  4/94 (4.26%)  6/94 (6.38%)  2/94 (2.13%) 
Psychiatric disorders       
Insomnia † 1  5/94 (5.32%)  4/94 (4.26%)  3/94 (3.19%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1  6/94 (6.38%)  2/94 (2.13%)  3/94 (3.19%) 
Skin and subcutaneous tissue disorders       
Rash † 1  12/94 (12.77%)  9/94 (9.57%)  4/94 (4.26%) 
Rash maculo-papular † 1  6/94 (6.38%)  7/94 (7.45%)  4/94 (4.26%) 
Dry skin † 1  11/94 (11.70%)  5/94 (5.32%)  4/94 (4.26%) 
Dermatitis † 1  6/94 (6.38%)  3/94 (3.19%)  1/94 (1.06%) 
Alopecia † 1  3/94 (3.19%)  5/94 (5.32%)  5/94 (5.32%) 
Hyperhidrosis † 1  3/94 (3.19%)  2/94 (2.13%)  5/94 (5.32%) 
Rash papular † 1  3/94 (3.19%)  5/94 (5.32%)  1/94 (1.06%) 
Vascular disorders       
Hypertension † 1  26/94 (27.66%)  32/94 (34.04%)  22/94 (23.40%) 
1
Term from vocabulary, MedDRA Version 22.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: TrialDisclosures@takeda.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02467270    
Other Study ID Numbers: AP24534-14-203
2014-001617-12 ( EudraCT Number )
15/LO/1192 ( Registry Identifier: NRES )
U1111-1238-0007 ( Other Grant/Funding Number: WHO )
First Submitted: June 2, 2015
First Posted: June 10, 2015
Results First Submitted: April 14, 2021
Results First Posted: June 14, 2021
Last Update Posted: February 6, 2024