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Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs

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ClinicalTrials.gov Identifier: NCT03106779
Recruitment Status : Active, not recruiting
First Posted : April 10, 2017
Results First Posted : February 15, 2022
Last Update Posted : April 24, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Myelogenous Leukemia
Interventions Drug: Asciminib
Drug: Bosutinib
Enrollment 233
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 Details Randomization was stratified by major cytogenetic response (MCyR) at screening.
Arm/Group Title Asciminib Bosutinib
Hide 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] 1 0
Completed [2] 97 22
Not Completed 60 54
Reason Not Completed
Lack of Efficacy             33             24
Adverse Event             8             16
Physician Decision             10             6
Patient/guardian decision             4             3
Progressive disease             1             3
Lost to Follow-up             1             2
Death             1             0
Protocol Violation             1             0
Not treated             1             0
[1]
One patient randomized to asciminib was discontinued due to cytopenia as per Investigator's decision and never took medication.
[2]
Completed = Patients ongoing at the time of the primary analysis cut-off
Arm/Group Title Asciminib Bosutinib Total
Hide Arm/Group Description Patients randomized to asciminib 40mg BID Patients randomized to bosutinib 500mg QD Total of all reporting groups
Overall Number of Baseline Participants 157 76 233
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): The FAS comprised of all randomized patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 157 participants 76 participants 233 participants
51.0  (13.49) 51.0  (13.95) 51.0  (13.61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 157 participants 76 participants 233 participants
Female
75
  47.8%
45
  59.2%
120
  51.5%
Male
82
  52.2%
31
  40.8%
113
  48.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 157 participants 76 participants 233 participants
White 118 56 174
Asian 22 11 33
Black or African American 8 2 10
American Indian or Alaska Native 1 0 1
Other 5 7 12
Unknown 3 0 3
1.Primary Outcome
Title Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS comprised of all randomized patients.
Arm/Group Title Asciminib Bosutinib
Hide Arm/Group Description:
Patients randomized to asciminib 40mg BID
Patients randomized to bosutinib 500mg QD
Overall Number of Participants Analyzed 157 76
Measure Type: Count of Participants
Unit of Measure: Participants
40
  25.5%
10
  13.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Asciminib, Bosutinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
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
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Major Molecular Response (MMR) Rate
Hide 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 Not Reported
3.Secondary Outcome
Title Complete Cytogenetic Response Rate
Hide 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 Not Reported
4.Secondary Outcome
Title Time to MMR
Hide 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 Not Reported
5.Secondary Outcome
Title Duration of MMR
Hide 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 Not Reported
6.Secondary Outcome
Title Time to CCyR
Hide 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 Not Reported
7.Secondary Outcome
Title Duration of CCyR
Hide 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 Not Reported
8.Secondary Outcome
Title Time to Treatment Failure
Hide 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 Not Reported
9.Secondary Outcome
Title Progression Free Survival
Hide 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 Not Reported
10.Secondary Outcome
Title Overall Survival
Hide 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 Not Reported
11.Secondary Outcome
Title Trough Plasma Concentrations
Hide 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 Not Reported
12.Secondary Outcome
Title PK Parameter: Cmax,
Hide 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 Not Reported
13.Secondary Outcome
Title PK Parameter: Tmax
Hide 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 Not Reported
14.Secondary Outcome
Title PK Parameter: AUC0-12h
Hide 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 Not Reported
15.Secondary Outcome
Title PK Parameter: CL/F
Hide 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 Not Reported
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
Hide Arm/Group Description Patients randomized to asciminib 40mg BID Patients randomized to bosutinib 500mg QD
All-Cause Mortality
Asciminib Bosutinib
Affected / at Risk (%) Affected / at Risk (%)
Total   4/156 (2.56%)   1/76 (1.32%) 
Hide Serious Adverse Events
Asciminib Bosutinib
Affected / at Risk (%) Affected / at Risk (%)
Total   21/156 (13.46%)   14/76 (18.42%) 
Blood and lymphatic system disorders     
Febrile neutropenia † 1  1/156 (0.64%)  0/76 (0.00%) 
Pancytopenia † 1  0/156 (0.00%)  1/76 (1.32%) 
Thrombocytopenia † 1  1/156 (0.64%)  0/76 (0.00%) 
Cardiac disorders     
Acute coronary syndrome † 1  0/156 (0.00%)  1/76 (1.32%) 
Atrial fibrillation † 1  0/156 (0.00%)  1/76 (1.32%) 
Cardiac failure † 1  1/156 (0.64%)  0/76 (0.00%) 
Cardiac failure congestive † 1  0/156 (0.00%)  1/76 (1.32%) 
Myocardial ischaemia † 1  1/156 (0.64%)  0/76 (0.00%) 
Eye disorders     
Toxic optic neuropathy † 1  1/156 (0.64%)  0/76 (0.00%) 
Gastrointestinal disorders     
Mesenteric artery embolism † 1  1/156 (0.64%)  0/76 (0.00%) 
Mesenteric artery thrombosis † 1  1/156 (0.64%)  0/76 (0.00%) 
Nausea † 1  1/156 (0.64%)  0/76 (0.00%) 
Stomatitis † 1  0/156 (0.00%)  1/76 (1.32%) 
Subileus † 1  1/156 (0.64%)  0/76 (0.00%) 
Vomiting † 1  1/156 (0.64%)  1/76 (1.32%) 
General disorders     
Hyperthermia † 1  1/156 (0.64%)  0/76 (0.00%) 
Non-cardiac chest pain † 1  1/156 (0.64%)  0/76 (0.00%) 
Pyrexia † 1  2/156 (1.28%)  0/76 (0.00%) 
Infections and infestations     
COVID-19 † 1  1/156 (0.64%)  0/76 (0.00%) 
Mycobacterium avium complex infection † 1  1/156 (0.64%)  0/76 (0.00%) 
Postoperative wound infection † 1  1/156 (0.64%)  0/76 (0.00%) 
Respiratory tract infection † 1  0/156 (0.00%)  1/76 (1.32%) 
Septic shock † 1  0/156 (0.00%)  1/76 (1.32%) 
Upper respiratory tract infection † 1  1/156 (0.64%)  0/76 (0.00%) 
Urinary tract infection † 1  1/156 (0.64%)  0/76 (0.00%) 
Injury, poisoning and procedural complications     
Rib fracture † 1  0/156 (0.00%)  1/76 (1.32%) 
Spinal compression fracture † 1  1/156 (0.64%)  0/76 (0.00%) 
Investigations     
Ejection fraction decreased † 1  1/156 (0.64%)  0/76 (0.00%) 
Platelet count decreased † 1  1/156 (0.64%)  0/76 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  0/156 (0.00%)  1/76 (1.32%) 
Dehydration † 1  1/156 (0.64%)  1/76 (1.32%) 
Musculoskeletal and connective tissue disorders     
Flank pain † 1  1/156 (0.64%)  0/76 (0.00%) 
Muscle spasms † 1  1/156 (0.64%)  0/76 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Diffuse large B-cell lymphoma † 1  0/156 (0.00%)  1/76 (1.32%) 
Squamous cell carcinoma † 1  0/156 (0.00%)  1/76 (1.32%) 
Nervous system disorders     
Headache † 1  1/156 (0.64%)  0/76 (0.00%) 
Hemiparesis † 1  0/156 (0.00%)  1/76 (1.32%) 
Ischaemic stroke † 1  1/156 (0.64%)  0/76 (0.00%) 
Product Issues     
Device malfunction † 1  1/156 (0.64%)  0/76 (0.00%) 
Psychiatric disorders     
Anxiety † 1  1/156 (0.64%)  0/76 (0.00%) 
Depression † 1  1/156 (0.64%)  0/76 (0.00%) 
Major depression † 1  1/156 (0.64%)  0/76 (0.00%) 
Renal and urinary disorders     
Acute kidney injury † 1  0/156 (0.00%)  1/76 (1.32%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure † 1  0/156 (0.00%)  1/76 (1.32%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic † 1  0/156 (0.00%)  1/76 (1.32%) 
Drug eruption † 1  0/156 (0.00%)  1/76 (1.32%) 
Rash † 1  0/156 (0.00%)  2/76 (2.63%) 
Vascular disorders     
Angiopathy † 1  1/156 (0.64%)  0/76 (0.00%) 
Aortic occlusion † 1  1/156 (0.64%)  0/76 (0.00%) 
Haematoma † 1  1/156 (0.64%)  0/76 (0.00%) 
1
Term from vocabulary, MedDRA (23.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Asciminib Bosutinib
Affected / at Risk (%) Affected / at Risk (%)
Total   122/156 (78.21%)   69/76 (90.79%) 
Blood and lymphatic system disorders     
Anaemia † 1  15/156 (9.62%)  6/76 (7.89%) 
Neutropenia † 1  28/156 (17.95%)  13/76 (17.11%) 
Thrombocytopenia † 1  35/156 (22.44%)  10/76 (13.16%) 
Gastrointestinal disorders     
Abdominal pain † 1  7/156 (4.49%)  11/76 (14.47%) 
Abdominal pain upper † 1  7/156 (4.49%)  5/76 (6.58%) 
Constipation † 1  8/156 (5.13%)  4/76 (5.26%) 
Diarrhoea † 1  18/156 (11.54%)  54/76 (71.05%) 
Dyspepsia † 1  8/156 (5.13%)  3/76 (3.95%) 
Nausea † 1  18/156 (11.54%)  35/76 (46.05%) 
Vomiting † 1  11/156 (7.05%)  19/76 (25.00%) 
General disorders     
Asthenia † 1  9/156 (5.77%)  1/76 (1.32%) 
Fatigue † 1  16/156 (10.26%)  7/76 (9.21%) 
Oedema peripheral † 1  9/156 (5.77%)  2/76 (2.63%) 
Pyrexia † 1  4/156 (2.56%)  6/76 (7.89%) 
Infections and infestations     
Nasopharyngitis † 1  15/156 (9.62%)  2/76 (2.63%) 
Upper respiratory tract infection † 1  10/156 (6.41%)  4/76 (5.26%) 
Investigations     
Alanine aminotransferase increased † 1  6/156 (3.85%)  21/76 (27.63%) 
Amylase increased † 1  9/156 (5.77%)  4/76 (5.26%) 
Aspartate aminotransferase increased † 1  6/156 (3.85%)  16/76 (21.05%) 
Lipase increased † 1  8/156 (5.13%)  5/76 (6.58%) 
Neutrophil count decreased † 1  7/156 (4.49%)  4/76 (5.26%) 
Platelet count decreased † 1  10/156 (6.41%)  4/76 (5.26%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  6/156 (3.85%)  6/76 (7.89%) 
Hypophosphataemia † 1  2/156 (1.28%)  4/76 (5.26%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  14/156 (8.97%)  1/76 (1.32%) 
Back pain † 1  10/156 (6.41%)  1/76 (1.32%) 
Pain in extremity † 1  10/156 (6.41%)  5/76 (6.58%) 
Nervous system disorders     
Dizziness † 1  10/156 (6.41%)  2/76 (2.63%) 
Headache † 1  25/156 (16.03%)  10/76 (13.16%) 
Psychiatric disorders     
Insomnia † 1  8/156 (5.13%)  1/76 (1.32%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  10/156 (6.41%)  4/76 (5.26%) 
Skin and subcutaneous tissue disorders     
Dry skin † 1  3/156 (1.92%)  6/76 (7.89%) 
Pruritus † 1  8/156 (5.13%)  5/76 (6.58%) 
Rash † 1  11/156 (7.05%)  17/76 (22.37%) 
Vascular disorders     
Hypertension † 1  18/156 (11.54%)  3/76 (3.95%) 
1
Term from vocabulary, MedDRA (23.0)
†
Indicates events were collected by systematic assessment
In the asciminib arm, 2 patients died on-treatment and 2 patients died during survival follow-up. In the bosutinib arm, 1 patient died on-treatment.
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 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
Layout table for Results Point of Contact information
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03106779    
Other Study ID Numbers: CABL001A2301
First Submitted: March 9, 2017
First Posted: April 10, 2017
Results First Submitted: November 27, 2021
Results First Posted: February 15, 2022
Last Update Posted: April 24, 2024