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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03106779
Collaborator
(none)
233
88
2
159
2.6
0

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

Study Type:
Interventional
Actual Enrollment :
233 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multi-center, Open-label, Randomized Study of Oral ABL001 Versus Bosutinib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors
Actual Study Start Date :
Sep 17, 2011
Actual Primary Completion Date :
May 25, 2020
Anticipated Study Completion Date :
Dec 18, 2024

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:
  • ABL001
  • 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

    1. 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

    1. 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

    2. 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.

    3. 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

    4. 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

    5. 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

    6. 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

    7. 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

    8. 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

    9. Overall Survival [96 weeks after the last patient received the first study dose]

      To compare additional parameters of the efficacy of asciminib versus bosutinib

    10. 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

    11. 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

    12. 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

    13. 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

    14. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03106779
    Other Study ID Numbers:
    • CABL001A2301
    First Posted:
    Apr 10, 2017
    Last Update Posted:
    Jul 14, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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
    6. Secondary Outcome
    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
    7. Secondary Outcome
    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
    8. Secondary Outcome
    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
    9. Secondary Outcome
    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
    10. Secondary Outcome
    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
    11. Secondary Outcome
    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
    12. Secondary Outcome
    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
    13. Secondary Outcome
    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
    14. Secondary Outcome
    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
    15. Secondary Outcome
    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

    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.

    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
    Email novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03106779
    Other Study ID Numbers:
    • CABL001A2301
    First Posted:
    Apr 10, 2017
    Last Update Posted:
    Jul 14, 2022
    Last Verified:
    Jun 1, 2022