Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs
Study Details
Study Description
Brief Summary
The purpose of this pivotal study was to compare the efficacy of asciminib (ABL001) with that of bosutinib in the treatment of patients with CML-CP having previously been treated with a minimum of two prior ATP-binding site TKIs.
Patients intolerant to the most recent TKI therapy must have had BCR-ABL1 ratio > 0.1% IS at screening and patients failing their most recent TKI therapy must have met the definition of treatment failure as per the 2013 European LeukemiaNet (ELN) recommendations.
Patients with documented treatment failure as per 2013 ELN recommendations while on bosutinib treatment had the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Detailed Description
Patients were randomized in a 2:1 ratio to asciminib 40 mg BID or bosutinib 500 mg QD. Randomization was stratified by major cytogenetic response (MCyR) at screening. Patients with documented treatment failure (specifically meeting lack of efficacy criteria adapted from the 2013 ELN recommendations) while on bosutinib treatment were offered the option to switch to asciminib treatment within 96 weeks after the last patient was randomized to the study.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Asciminib Patients were randomized to asciminib 40mg BID |
Drug: Asciminib
40 mg tablets was taken orally twice a day (BID)
Other Names:
|
Active Comparator: Bosutinib Patients were randomized to bosutinib 500mg QD |
Drug: Bosutinib
500 mg tablets was taken orally once daily (QD)
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks [24 weeks]
MMR was defined as a ≥ 3.0 log reduction in BCR-ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1% BCR-ABL1/ABL% by IS as measured by RQ-PCR.
Secondary Outcome Measures
- Number of Participants With Major Molecular Response (MMR) Rate [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy asciminib versus bosutinib
- Complete Cytogenetic Response Rate [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib. Cytogenic response will include Complete, Partial, Major, Minor, Minimal and no response.
- Time to MMR [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Duration of MMR [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Time to CCyR [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Duration of CCyR [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Time to Treatment Failure [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Progression Free Survival [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Overall Survival [96 weeks after the last patient received the first study dose]
To compare additional parameters of the efficacy of asciminib versus bosutinib
- Trough Plasma Concentrations [96 weeks after the last patient received the first study dose]
To characterize the PK of asciminib in the CML-CP population
- PK Parameter: Cmax, [96 weeks after the last patient received the first study dose]
To characterize the PK of asciminib in the CML-CP population
- PK Parameter: Tmax [96 weeks after the last patient received the first study dose]
To characterize the PK of asciminib in the CML-CP population
- PK Parameter: AUC0-12h [96 weeks after the last patient received the first study dose]
To characterize the PK of asciminib in the CML-CP population
- PK Parameter: CL/F [96 weeks after the last patient received the first study dose]
To characterize the PK of asciminib in the CML-CP population
Eligibility Criteria
Criteria
Inclusion Criteria:
Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
Patients must meet all of the following laboratory values at the screening visit:
-
< 15% blasts in peripheral blood and bone marrow
-
< 30% blasts plus promyelocytes in peripheral blood and bone marrow
-
< 20% basophils in the peripheral blood
-
≥ 50 x 109/L (≥ 50,000/mm3) platelets
-
Transient prior therapy related thrombocytopenia (< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable
-
No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
BCR-ABL1 ratio > 0.1% IS according to central laboratory at the screening examination for patients intolerant to the most recent TKI therapy
Prior treatment with a minimum of 2 prior ATP-binding site TKIs (i.e. imatinib, nilotinib, dasatinib, radotinib or ponatinib)
Failure (adapted from the 2013 ELN Guidelines Bacarrani 2013) or intolerance to the most recent TKI therapy at the time of screening
-
Failure is defined for CML-CP patients (CP at the time of initiation of last therapy) as follows. Patients must meet at least 1 of the following criteria.
-
Three months after the initiation of therapy: No CHR or > 95% Ph+ metaphases
-
Six months after the initiation of therapy: BCR-ABL1 ratio > 10% IS and/or > 65% Ph+ metaphases
-
Twelve months after initiation of therapy: BCR-ABL1 ratio > 10% IS and/or > 35% Ph+ metaphases
-
At any time after the initiation of therapy, loss of CHR, CCyR or PCyR
-
At any time after the initiation of therapy, the development of new BCR-ABL1 mutations which potentially cause resistance to study treatment
-
At any time after the initiation of therapy, confirmed loss of MMR in 2 consecutive tests, of which one must have a BCR-ABL1 ratio ≥ 1% IS
-
At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: CCA/Ph+
-
Intolerance is defined as:
-
Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)
-
Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer
Exclusion Criteria:
Known presence of the T315I or V299L mutation at any time prior to study entry Known second chronic phase of CML after previous progression to AP/BC Previous treatment with a hematopoietic stem-cell transplantation Patient planning to undergo allogeneic hematopoietic stem cell transplantation
Cardiac or cardiac repolarization abnormality, including any of the following:
-
History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
-
Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
-
QTcF at screening ≥450 msec (male patients), ≥460 msec (female patients)
-
Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
-
Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
-
Concomitant medication(s) with a known risk of Torsades de Pointes per www.crediblemeds.org that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
-
Inability to determine the QTcF interval
-
Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, pulmonary hypertension)
-
History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
-
History of acute or chronic liver disease
-
Treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with study treatment
-
Moderate or strong inducers of CYP3A
-
Moderate or strong inhibitors of CYP3A
-
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 days after last dose of ABL001 and one month after last dose of bosutinib. Highly effective contraception methods include:
-
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
-
Female sterilization (have had surgical bilateral oophorectomy (with or without hysterectomy) total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
-
Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.
-
Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
-
In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
-
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking study medication. In the case of oophorectomy alone, women are considered post-menopausal and not of child bearing potential only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Chicago Hospital | Chicago | Illinois | United States | 60637 |
2 | Indiana Blood and Marrow Institute Regulatory - 2 | Beech Grove | Indiana | United States | 46107 |
3 | Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | United States | 21205 |
4 | Dana Farber Cancer Center | Boston | Massachusetts | United States | 02215 |
5 | University of Michigan Clinical Trials Office Main Site | Ann Arbor | Michigan | United States | 48109 |
6 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
7 | Weill Cornell Medicine NewYork Presbyterian Hospital | New York | New York | United States | 10021 |
8 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
9 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
10 | Utah Huntsman Cancer Center | Salt Lake City | Utah | United States | 84112 |
11 | Novartis Investigative Site | Caba | Buenos Aires | Argentina | C1221ADH |
12 | Novartis Investigative Site | Capital Federal | Argentina | C1114AAN | |
13 | Novartis Investigative Site | Cordoba | Argentina | X5016KEH | |
14 | Novartis Investigative Site | Adelaide | South Australia | Australia | 5000 |
15 | Novartis Investigative Site | Melbourne | Victoria | Australia | 3000 |
16 | Novartis Investigative Site | Murdoch | Western Australia | Australia | 6150 |
17 | Novartis Investigative Site | Rio de Janeiro | RJ | Brazil | 20.211-030 |
18 | Novartis Investigative Site | Sao Paulo | SP | Brazil | 05403 000 |
19 | Novartis Investigative Site | Sao Paulo | SP | Brazil | 08270-070 |
20 | Novartis Investigative Site | Porto Alegre | Brazil | 90035-003 | |
21 | Novartis Investigative Site | Plovdiv | Bulgaria | 4002 | |
22 | Novartis Investigative Site | Varna | Bulgaria | 9000 | |
23 | Novartis Investigative Site | Toronto | Ontario | Canada | M5G 2M9 |
24 | Novartis Investigative Site | Ostrava Poruba | Czech Republic | Czechia | 708 52 |
25 | Novartis Investigative Site | Brno Bohunice | Czechia | 625 00 | |
26 | Novartis Investigative Site | Bordeaux | France | 33076 | |
27 | Novartis Investigative Site | Lyon Cedex | France | 69373 | |
28 | Novartis Investigative Site | Marseille | France | 13273 | |
29 | Novartis Investigative Site | Paris Cedex 10 | France | 75475 | |
30 | Novartis Investigative Site | Vandoeuvre les Nancy | France | 54511 | |
31 | Novartis Investigative Site | Mannheim | Baden-Wuerttemberg | Germany | 68305 |
32 | Novartis Investigative Site | Berlin | Germany | 13353 | |
33 | Novartis Investigative Site | Duesseldorf | Germany | 40225 | |
34 | Novartis Investigative Site | Frankfurt | Germany | 60590 | |
35 | Novartis Investigative Site | Heidelberg | Germany | 69120 | |
36 | Novartis Investigative Site | Jena | Germany | 07740 | |
37 | Novartis Investigative Site | Kiel | Germany | 24116 | |
38 | Novartis Investigative Site | Budapest | Hungary | 1097 | |
39 | Novartis Investigative Site | Debrecen | Hungary | 4032 | |
40 | Novartis Investigative Site | Jerusalem | Israel | 9112001 | |
41 | Novartis Investigative Site | Zrifin | Israel | 70300 | |
42 | Novartis Investigative Site | Bari | BA | Italy | 70124 |
43 | Novartis Investigative Site | Milano | MI | Italy | 20122 |
44 | Novartis Investigative Site | Napoli | Italy | 80132 | |
45 | Novartis Investigative Site | Nagoya | Aichi | Japan | 453-8511 |
46 | Novartis Investigative Site | Toyoake city | Aichi | Japan | 470 1192 |
47 | Novartis Investigative Site | Kashiwa | Chiba | Japan | 277 8577 |
48 | Novartis Investigative Site | Kobe-shi | Hyogo | Japan | 650-0017 |
49 | Novartis Investigative Site | Osaka Sayama | Osaka | Japan | 589 8511 |
50 | Novartis Investigative Site | Suita city | Osaka | Japan | 565 0871 |
51 | Novartis Investigative Site | Bunkyo ku | Tokyo | Japan | 113-8677 |
52 | Novartis Investigative Site | Chuo-city | Yamanashi | Japan | 409-3898 |
53 | Novartis Investigative Site | Akita | Japan | 010-8543 | |
54 | Novartis Investigative Site | Aomori | Japan | 030 8553 | |
55 | Novartis Investigative Site | Uijeongbu si | Gyeonggi Do | Korea, Republic of | 11759 |
56 | Novartis Investigative Site | Seoul | Seocho Gu | Korea, Republic of | 06591 |
57 | Novartis Investigative Site | Busan | Korea, Republic of | 49201 | |
58 | Novartis Investigative Site | Jeollanam-do | Korea, Republic of | 519763 | |
59 | Novartis Investigative Site | Ashrafieh | Lebanon | 166830 | |
60 | Novartis Investigative Site | Beirut | Lebanon | 1107 2020 | |
61 | Novartis Investigative Site | Monterrey | Nuevo Leon | Mexico | 64460 |
62 | Novartis Investigative Site | Amsterdam | Netherlands | 1081 HV | |
63 | Novartis Investigative Site | Dordrecht | Netherlands | 3318AT | |
64 | Novartis Investigative Site | Cluj-Napoca | Romania | 400124 | |
65 | Novartis Investigative Site | Timisoara | Romania | 300079 | |
66 | Novartis Investigative Site | Moscow | Russian Federation | 125167 | |
67 | Novartis Investigative Site | Moscow | Russian Federation | 125284 | |
68 | Novartis Investigative Site | Saint Petersburg | Russian Federation | 191024 | |
69 | Novartis Investigative Site | Saint Petersburg | Russian Federation | 197341 | |
70 | Novartis Investigative Site | Riyadh | Saudi Arabia | 11211 | |
71 | Novartis Investigative Site | Belgrade | Serbia | 11000 | |
72 | Novartis Investigative Site | Novi Sad | Serbia | ||
73 | Novartis Investigative Site | Bilbao | Bizkaia | Spain | 48013 |
74 | Novartis Investigative Site | Toledo | Castilla La Mancha | Spain | 45071 |
75 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08036 |
76 | Novartis Investigative Site | Hospitalet de LLobregat | Catalunya | Spain | 08907 |
77 | Novartis Investigative Site | Madrid | Spain | 28034 | |
78 | Novartis Investigative Site | Zürich | Switzerland | 8091 | |
79 | Novartis Investigative Site | Istanbul | TUR | Turkey | 34098 |
80 | Novartis Investigative Site | Adana | Turkey | 01330 | |
81 | Novartis Investigative Site | Istanbul | Turkey | 34093 | |
82 | Novartis Investigative Site | Izmir | Turkey | 35040 | |
83 | Novartis Investigative Site | Samsun | Turkey | 55139 | |
84 | Novartis Investigative Site | Wirral | Merseyside | United Kingdom | CH63 4JY |
85 | Novartis Investigative Site | Glasgow | Scotland | United Kingdom | G12 0YN |
86 | Novartis Investigative Site | Cardiff | United Kingdom | CF4 4XN | |
87 | Novartis Investigative Site | London | United Kingdom | W12 0HS | |
88 | Novartis Investigative Site | Oxford | United Kingdom | OX3 7LJ |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.- CABL001A2301
Study Results
Participant Flow
Recruitment Details | Approximately 220 patients were planned to be enrolled, and 233 patients (157 randomized to treatment with asciminib and 76 to treatment with bosutinib) were enrolled and analyzed |
---|---|
Pre-assignment Detail | Randomization was stratified by major cytogenetic response (MCyR) at screening. |
Arm/Group Title | Asciminib | Bosutinib |
---|---|---|
Arm/Group Description | Patients randomized to asciminib 40mg BID | Patients randomized to bosutinib 500mg QD |
Period Title: Overall Study | ||
STARTED | 157 | 76 |
Treated | 156 | 0 |
Not Treated | 1 | 0 |
COMPLETED | 97 | 22 |
NOT COMPLETED | 60 | 54 |
Baseline Characteristics
Arm/Group Title | Asciminib | Bosutinib | Total |
---|---|---|---|
Arm/Group Description | Patients randomized to asciminib 40mg BID | Patients randomized to bosutinib 500mg QD | Total of all reporting groups |
Overall Participants | 157 | 76 | 233 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
51.0
(13.49)
|
51.0
(13.95)
|
51.0
(13.61)
|
Sex: Female, Male (Count of Participants) | |||
Female |
75
47.8%
|
45
59.2%
|
120
51.5%
|
Male |
82
52.2%
|
31
40.8%
|
113
48.5%
|
Race/Ethnicity, Customized (participants) [Number] | |||
White |
118
75.2%
|
56
73.7%
|
174
74.7%
|
Asian |
22
14%
|
11
14.5%
|
33
14.2%
|
Black or African American |
8
5.1%
|
2
2.6%
|
10
4.3%
|
American Indian or Alaska Native |
1
0.6%
|
0
0%
|
1
0.4%
|
Other |
5
3.2%
|
7
9.2%
|
12
5.2%
|
Unknown |
3
1.9%
|
0
0%
|
3
1.3%
|
Outcome Measures
Title | Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks |
---|---|
Description | MMR was defined as a ≥ 3.0 log reduction in BCR-ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1% BCR-ABL1/ABL% by IS as measured by RQ-PCR. |
Time Frame | 24 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set (FAS): The FAS comprised of all randomized patients. |
Arm/Group Title | Asciminib | Bosutinib |
---|---|---|
Arm/Group Description | Patients randomized to asciminib 40mg BID | Patients randomized to bosutinib 500mg QD |
Measure Participants | 157 | 76 |
Count of Participants [Participants] |
40
25.5%
|
10
13.2%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Asciminib, Bosutinib |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.029 |
Comments | ||
Method | Cochran-Mantel-Haenszel | |
Comments | Stratified by the randomization stratification factor, i.e. cytogenetic response status (MCyR vs no MCyR) at screening | |
Method of Estimation | Estimation Parameter | treatment difference in the MMR rate |
Estimated Value | 12.2 | |
Confidence Interval |
(2-Sided) 95% 2.19 to 22.30 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Number of Participants With Major Molecular Response (MMR) Rate |
---|---|
Description | To compare additional parameters of the efficacy asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Complete Cytogenetic Response Rate |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib. Cytogenic response will include Complete, Partial, Major, Minor, Minimal and no response. |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Time to MMR |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Duration of MMR |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Time to CCyR |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Duration of CCyR |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Time to Treatment Failure |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Progression Free Survival |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Overall Survival |
---|---|
Description | To compare additional parameters of the efficacy of asciminib versus bosutinib |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Trough Plasma Concentrations |
---|---|
Description | To characterize the PK of asciminib in the CML-CP population |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | PK Parameter: Cmax, |
---|---|
Description | To characterize the PK of asciminib in the CML-CP population |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | PK Parameter: Tmax |
---|---|
Description | To characterize the PK of asciminib in the CML-CP population |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | PK Parameter: AUC0-12h |
---|---|
Description | To characterize the PK of asciminib in the CML-CP population |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | PK Parameter: CL/F |
---|---|
Description | To characterize the PK of asciminib in the CML-CP population |
Time Frame | 96 weeks after the last patient received the first study dose |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | For this interim results, Adverse Events were reported from informed consent (maximum 21 days before randomization) until end of treatment plus 30 days. The maximum duration of treatment exposure was 129.9 weeks for asciminib and 117 weeks for bosutinib. | |||
---|---|---|---|---|
Adverse Event Reporting Description | Adverse Event (AE): Any sign or symptom that occurs during treatment plus 30 days after study treatment discontinuation. Adverse events were analyzed in the Safety analysis set, which comprises all patients who received at least one dose of study treatment. | |||
Arm/Group Title | Asciminib | Bosutinib | ||
Arm/Group Description | Patients randomized to asciminib 40mg BID | Patients randomized to bosutinib 500mg QD | ||
All Cause Mortality |
||||
Asciminib | Bosutinib | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/156 (2.6%) | 1/76 (1.3%) | ||
Serious Adverse Events |
||||
Asciminib | Bosutinib | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 21/156 (13.5%) | 14/76 (18.4%) | ||
Blood and lymphatic system disorders | ||||
Febrile neutropenia | 1/156 (0.6%) | 0/76 (0%) | ||
Pancytopenia | 0/156 (0%) | 1/76 (1.3%) | ||
Thrombocytopenia | 1/156 (0.6%) | 0/76 (0%) | ||
Cardiac disorders | ||||
Acute coronary syndrome | 0/156 (0%) | 1/76 (1.3%) | ||
Atrial fibrillation | 0/156 (0%) | 1/76 (1.3%) | ||
Cardiac failure | 1/156 (0.6%) | 0/76 (0%) | ||
Cardiac failure congestive | 0/156 (0%) | 1/76 (1.3%) | ||
Myocardial ischaemia | 1/156 (0.6%) | 0/76 (0%) | ||
Eye disorders | ||||
Toxic optic neuropathy | 1/156 (0.6%) | 0/76 (0%) | ||
Gastrointestinal disorders | ||||
Mesenteric artery embolism | 1/156 (0.6%) | 0/76 (0%) | ||
Mesenteric artery thrombosis | 1/156 (0.6%) | 0/76 (0%) | ||
Nausea | 1/156 (0.6%) | 0/76 (0%) | ||
Stomatitis | 0/156 (0%) | 1/76 (1.3%) | ||
Subileus | 1/156 (0.6%) | 0/76 (0%) | ||
Vomiting | 1/156 (0.6%) | 1/76 (1.3%) | ||
General disorders | ||||
Hyperthermia | 1/156 (0.6%) | 0/76 (0%) | ||
Non-cardiac chest pain | 1/156 (0.6%) | 0/76 (0%) | ||
Pyrexia | 2/156 (1.3%) | 0/76 (0%) | ||
Infections and infestations | ||||
COVID-19 | 1/156 (0.6%) | 0/76 (0%) | ||
Mycobacterium avium complex infection | 1/156 (0.6%) | 0/76 (0%) | ||
Postoperative wound infection | 1/156 (0.6%) | 0/76 (0%) | ||
Respiratory tract infection | 0/156 (0%) | 1/76 (1.3%) | ||
Septic shock | 0/156 (0%) | 1/76 (1.3%) | ||
Upper respiratory tract infection | 1/156 (0.6%) | 0/76 (0%) | ||
Urinary tract infection | 1/156 (0.6%) | 0/76 (0%) | ||
Injury, poisoning and procedural complications | ||||
Rib fracture | 0/156 (0%) | 1/76 (1.3%) | ||
Spinal compression fracture | 1/156 (0.6%) | 0/76 (0%) | ||
Investigations | ||||
Ejection fraction decreased | 1/156 (0.6%) | 0/76 (0%) | ||
Platelet count decreased | 1/156 (0.6%) | 0/76 (0%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 0/156 (0%) | 1/76 (1.3%) | ||
Dehydration | 1/156 (0.6%) | 1/76 (1.3%) | ||
Musculoskeletal and connective tissue disorders | ||||
Flank pain | 1/156 (0.6%) | 0/76 (0%) | ||
Muscle spasms | 1/156 (0.6%) | 0/76 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Diffuse large B-cell lymphoma | 0/156 (0%) | 1/76 (1.3%) | ||
Squamous cell carcinoma | 0/156 (0%) | 1/76 (1.3%) | ||
Nervous system disorders | ||||
Headache | 1/156 (0.6%) | 0/76 (0%) | ||
Hemiparesis | 0/156 (0%) | 1/76 (1.3%) | ||
Ischaemic stroke | 1/156 (0.6%) | 0/76 (0%) | ||
Product Issues | ||||
Device malfunction | 1/156 (0.6%) | 0/76 (0%) | ||
Psychiatric disorders | ||||
Anxiety | 1/156 (0.6%) | 0/76 (0%) | ||
Depression | 1/156 (0.6%) | 0/76 (0%) | ||
Major depression | 1/156 (0.6%) | 0/76 (0%) | ||
Renal and urinary disorders | ||||
Acute kidney injury | 0/156 (0%) | 1/76 (1.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Respiratory failure | 0/156 (0%) | 1/76 (1.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Dermatitis allergic | 0/156 (0%) | 1/76 (1.3%) | ||
Drug eruption | 0/156 (0%) | 1/76 (1.3%) | ||
Rash | 0/156 (0%) | 2/76 (2.6%) | ||
Vascular disorders | ||||
Angiopathy | 1/156 (0.6%) | 0/76 (0%) | ||
Aortic occlusion | 1/156 (0.6%) | 0/76 (0%) | ||
Haematoma | 1/156 (0.6%) | 0/76 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Asciminib | Bosutinib | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 122/156 (78.2%) | 69/76 (90.8%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 15/156 (9.6%) | 6/76 (7.9%) | ||
Neutropenia | 28/156 (17.9%) | 13/76 (17.1%) | ||
Thrombocytopenia | 35/156 (22.4%) | 10/76 (13.2%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 7/156 (4.5%) | 11/76 (14.5%) | ||
Abdominal pain upper | 7/156 (4.5%) | 5/76 (6.6%) | ||
Constipation | 8/156 (5.1%) | 4/76 (5.3%) | ||
Diarrhoea | 18/156 (11.5%) | 54/76 (71.1%) | ||
Dyspepsia | 8/156 (5.1%) | 3/76 (3.9%) | ||
Nausea | 18/156 (11.5%) | 35/76 (46.1%) | ||
Vomiting | 11/156 (7.1%) | 19/76 (25%) | ||
General disorders | ||||
Asthenia | 9/156 (5.8%) | 1/76 (1.3%) | ||
Fatigue | 16/156 (10.3%) | 7/76 (9.2%) | ||
Oedema peripheral | 9/156 (5.8%) | 2/76 (2.6%) | ||
Pyrexia | 4/156 (2.6%) | 6/76 (7.9%) | ||
Infections and infestations | ||||
Nasopharyngitis | 15/156 (9.6%) | 2/76 (2.6%) | ||
Upper respiratory tract infection | 10/156 (6.4%) | 4/76 (5.3%) | ||
Investigations | ||||
Alanine aminotransferase increased | 6/156 (3.8%) | 21/76 (27.6%) | ||
Amylase increased | 9/156 (5.8%) | 4/76 (5.3%) | ||
Aspartate aminotransferase increased | 6/156 (3.8%) | 16/76 (21.1%) | ||
Lipase increased | 8/156 (5.1%) | 5/76 (6.6%) | ||
Neutrophil count decreased | 7/156 (4.5%) | 4/76 (5.3%) | ||
Platelet count decreased | 10/156 (6.4%) | 4/76 (5.3%) | ||
Metabolism and nutrition disorders | ||||
Decreased appetite | 6/156 (3.8%) | 6/76 (7.9%) | ||
Hypophosphataemia | 2/156 (1.3%) | 4/76 (5.3%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 14/156 (9%) | 1/76 (1.3%) | ||
Back pain | 10/156 (6.4%) | 1/76 (1.3%) | ||
Pain in extremity | 10/156 (6.4%) | 5/76 (6.6%) | ||
Nervous system disorders | ||||
Dizziness | 10/156 (6.4%) | 2/76 (2.6%) | ||
Headache | 25/156 (16%) | 10/76 (13.2%) | ||
Psychiatric disorders | ||||
Insomnia | 8/156 (5.1%) | 1/76 (1.3%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 10/156 (6.4%) | 4/76 (5.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Dry skin | 3/156 (1.9%) | 6/76 (7.9%) | ||
Pruritus | 8/156 (5.1%) | 5/76 (6.6%) | ||
Rash | 11/156 (7.1%) | 17/76 (22.4%) | ||
Vascular disorders | ||||
Hypertension | 18/156 (11.5%) | 3/76 (3.9%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title | Clinical Disclosure Office |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 862-778-8300 |
novartis.email@novartis.com |
- CABL001A2301