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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03106779




Registration number
NCT03106779
Ethics application status
Date submitted
9/03/2017
Date registered
10/04/2017

Titles & IDs
Public title
Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs
Scientific 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
Secondary ID [1] 0 0
CABL001A2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myelogenous Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Asciminib
Treatment: Drugs - Bosutinib

Experimental: Asciminib - Patients were randomized to asciminib 40mg BID

Active comparator: Bosutinib - Patients were randomized to bosutinib 500mg QD


Treatment: Drugs: Asciminib
40 mg tablets was taken orally twice a day (BID)

Treatment: Drugs: Bosutinib
500 mg tablets was taken orally once daily (QD)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Major Molecular Response (MMR) Rate at 24 Weeks
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Number of Participants With Major Molecular Response (MMR) Rate
Timepoint [1] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [2] 0 0
Complete Cytogenetic Response Rate
Timepoint [2] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [3] 0 0
Time to MMR
Timepoint [3] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [4] 0 0
Duration of MMR
Timepoint [4] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [5] 0 0
Time to CCyR
Timepoint [5] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [6] 0 0
Duration of CCyR
Timepoint [6] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [7] 0 0
Time to Treatment Failure
Timepoint [7] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [8] 0 0
Progression Free Survival
Timepoint [8] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [9] 0 0
Overall Survival
Timepoint [9] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [10] 0 0
Trough Plasma Concentrations
Timepoint [10] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [11] 0 0
PK Parameter: Cmax,
Timepoint [11] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [12] 0 0
PK Parameter: Tmax
Timepoint [12] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [13] 0 0
PK Parameter: AUC0-12h
Timepoint [13] 0 0
96 weeks after the last patient received the first study dose
Secondary outcome [14] 0 0
PK Parameter: CL/F
Timepoint [14] 0 0
96 weeks after the last patient received the first study dose

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/12/2024
Actual
Sample size
Target
Accrual to date
Final
233
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [3] 0 0
Novartis Investigative Site - Murdoch
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Capital Federal
Country [11] 0 0
Argentina
State/province [11] 0 0
Cordoba
Country [12] 0 0
Brazil
State/province [12] 0 0
RJ
Country [13] 0 0
Brazil
State/province [13] 0 0
SP
Country [14] 0 0
Brazil
State/province [14] 0 0
Porto Alegre
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Plovdiv
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Varna
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Czechia
State/province [18] 0 0
Poruba
Country [19] 0 0
Czechia
State/province [19] 0 0
Brno Bohunice
Country [20] 0 0
France
State/province [20] 0 0
Bordeaux
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Paris 10
Country [24] 0 0
France
State/province [24] 0 0
Vandoeuvre Les Nancy
Country [25] 0 0
Germany
State/province [25] 0 0
Baden Wuerttemberg
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Duesseldorf
Country [28] 0 0
Germany
State/province [28] 0 0
Frankfurt
Country [29] 0 0
Germany
State/province [29] 0 0
Heidelberg
Country [30] 0 0
Germany
State/province [30] 0 0
Jena
Country [31] 0 0
Germany
State/province [31] 0 0
Kiel
Country [32] 0 0
Hungary
State/province [32] 0 0
Budapest
Country [33] 0 0
Hungary
State/province [33] 0 0
Debrecen
Country [34] 0 0
Israel
State/province [34] 0 0
Jerusalem
Country [35] 0 0
Israel
State/province [35] 0 0
Zerifin
Country [36] 0 0
Italy
State/province [36] 0 0
BA
Country [37] 0 0
Italy
State/province [37] 0 0
MI
Country [38] 0 0
Italy
State/province [38] 0 0
Napoli
Country [39] 0 0
Japan
State/province [39] 0 0
Aichi
Country [40] 0 0
Japan
State/province [40] 0 0
Chiba
Country [41] 0 0
Japan
State/province [41] 0 0
Osaka
Country [42] 0 0
Japan
State/province [42] 0 0
Tokyo
Country [43] 0 0
Japan
State/province [43] 0 0
Yamanashi
Country [44] 0 0
Japan
State/province [44] 0 0
Akita
Country [45] 0 0
Japan
State/province [45] 0 0
Aomori
Country [46] 0 0
Japan
State/province [46] 0 0
Kobe-shi
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Gyeonggi Do
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Seocho Gu
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Busan
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Jeollanam
Country [51] 0 0
Lebanon
State/province [51] 0 0
Ashrafieh
Country [52] 0 0
Lebanon
State/province [52] 0 0
Beirut
Country [53] 0 0
Mexico
State/province [53] 0 0
Nuevo Leon
Country [54] 0 0
Netherlands
State/province [54] 0 0
Breda
Country [55] 0 0
Netherlands
State/province [55] 0 0
Groningen
Country [56] 0 0
Romania
State/province [56] 0 0
Cluj-Napoca
Country [57] 0 0
Romania
State/province [57] 0 0
Timisoara
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Moscow
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Saint Petersburg
Country [60] 0 0
Saudi Arabia
State/province [60] 0 0
Riyadh
Country [61] 0 0
Serbia
State/province [61] 0 0
Belgrade
Country [62] 0 0
Serbia
State/province [62] 0 0
Novi Sad
Country [63] 0 0
Spain
State/province [63] 0 0
Castilla La Mancha
Country [64] 0 0
Spain
State/province [64] 0 0
Catalunya
Country [65] 0 0
Spain
State/province [65] 0 0
Pais Vasco
Country [66] 0 0
Spain
State/province [66] 0 0
Madrid
Country [67] 0 0
Switzerland
State/province [67] 0 0
Zuerich
Country [68] 0 0
Turkey
State/province [68] 0 0
TUR
Country [69] 0 0
Turkey
State/province [69] 0 0
Adana
Country [70] 0 0
Turkey
State/province [70] 0 0
Istanbul
Country [71] 0 0
Turkey
State/province [71] 0 0
Izmir
Country [72] 0 0
Turkey
State/province [72] 0 0
Samsun
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Cardiff
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Glasgow
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Liverpool
Country [76] 0 0
United Kingdom
State/province [76] 0 0
London
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03106779