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

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

ClinicalTrials.gov Identifier: NCT03106779

Novartis Reference Number: CABL001A2301

See if you pre-qualify

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this pivotal study is to compare the efficacy of 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 BCR-ABL1 ratio > 0.1% IS at screening and patients failing their most recent TKI therapy must meet the definition of treatment failure as per the 2013 ELN guidelines.

Patients with documented treatment failure while on bosutinib treatment will have the option to switch to asciminib treatment within 96 weeks after the last patient has been randomized on study.

Condition 
Chronic Myelogenous Leukemia
Phase 
Phase 3
Overall status 
Recruiting
Enrollment count 
222 participants
Start date 
Oct 26, 2017
Completion date 
Jan 15, 2025
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
ABL001
40 mg tablets will be taken orally twice a day (BID)
Drug
Bosutinib
500 mg tablets will be taken orally once daily (QD)

Eligibility 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.

Study Locations

United States
Mayo Clinic Arizona
Withdrawn
Phoenix, 85054
Arizona
United States
City of Hope
Withdrawn
Duarte, 91010
California
United States
USC Norris Comprehensive Cancer Center
Withdrawn
Los Angeles, 90033
California
United States
University of Chicago Hospital
Active, not recruiting
Chicago, 60637
Illinois
United States
Indiana Blood and Marrow Institute Regulatory - 2
Active, not recruiting
Beech Grove, 46107
Indiana
United States
Sidney Kimmel Comprehensive Cancer Center
Active, not recruiting
Baltimore, 21205
Maryland
United States
Dana Farber Cancer Center
Active, not recruiting
Boston, 02215
Massachusetts
United States
University of Michigan Clinical Trials Office Main Site
Active, not recruiting
Ann Arbor, 48109
Michigan
United States
Washington U School of Medicine Center for Clinical Studies Main Site
Withdrawn
Saint Louis, 63110
Missouri
United States
Hackensack University Medical Center John Theurer Cancer Center
Withdrawn
Hackensack, 07601
New Jersey
United States
Roswell Park Cancer Institute
Active, not recruiting
Buffalo, 14263
New York
United States
Weill Cornell Medicine NewYork Presbyterian Hospital
Active, not recruiting
New York, 10021
New York
United States
Memorial Sloan Kettering Cancer Center
Active, not recruiting
New York, 10065
New York
United States
Oregon Health Sciences Univ Oregon Health Sciences Univ
Withdrawn
Portland, 97239
Oregon
United States
Houston Methodist Cancer Center
Withdrawn
Houston, 77030
Texas
United States
University of TX MD Anderson Cancer Center Primary
Active, not recruiting
Houston, 77030
Texas
United States
Utah Huntsman Cancer Center
Active, not recruiting
Salt Lake City, 84112
Utah
United States
Fred Hutchinson Cancer Center
Withdrawn
Seattle, 98109
Washington
United States
Argentina
Novartis Investigative Site
Active, not recruiting
Caba, C1221ADH
Buenos Aires
Argentina
Novartis Investigative Site
Withdrawn
La Plata, B1900AWT
Buenos Aires
Argentina
Novartis Investigative Site
Active, not recruiting
Capital Federal, C1114AAN
-
Argentina
Novartis Investigative Site
Active, not recruiting
Cordoba, X5016KEH
-
Argentina
Australia
Novartis Investigative Site
Withdrawn
Darlinghurst, 2010
New South Wales
Australia
Novartis Investigative Site
Active, not recruiting
Adelaide, 5000
South Australia
Australia
Novartis Investigative Site
Active, not recruiting
Melbourne, 3000
Victoria
Australia
Novartis Investigative Site
Active, not recruiting
Murdoch, 6150
Western Australia
Australia
Belgium
Novartis Investigative Site
Withdrawn
Brugge, 8000
-
Belgium
Novartis Investigative Site
Withdrawn
Leuven, 3000
-
Belgium
Brazil
Novartis Investigative Site
Active, not recruiting
Rio de Janeiro, 20.211-030
RJ
Brazil
Novartis Investigative Site
Active, not recruiting
Sao Paulo, 05403 000
SP
Brazil
Novartis Investigative Site
Active, not recruiting
Sao Paulo, 08270-070
SP
Brazil
Novartis Investigative Site
Active, not recruiting
Porto Alegre, 90035-003
-
Brazil
Bulgaria
Novartis Investigative Site
Active, not recruiting
Pleven, 5800
-
Bulgaria
Novartis Investigative Site
Completed
Plovdiv, 4002
-
Bulgaria
Novartis Investigative Site
Withdrawn
Sofia, 1756
-
Bulgaria
Novartis Investigative Site
Active, not recruiting
Varna, 9000
-
Bulgaria
Canada
Novartis Investigative Site
Active, not recruiting
Toronto, M5G 2M9
Ontario
Canada
Novartis Investigative Site
Withdrawn
Montreal, H3T 1E2
Quebec
Canada
Czechia
Novartis Investigative Site
Active, not recruiting
Ostrava Poruba, 708 52
Czech Republic
Czechia
Novartis Investigative Site
Withdrawn
Praha 2, 128 20
Czech Republic
Czechia
Novartis Investigative Site
Withdrawn
Hradec Kralove, 500 05
CZE
Czechia
Novartis Investigative Site
Active, not recruiting
Brno Bohunice, 625 00
-
Czechia
France
Novartis Investigative Site
Active, not recruiting
Bordeaux, 33076
-
France
Novartis Investigative Site
Withdrawn
Lille Cedex, 59037
-
France
Novartis Investigative Site
Active, not recruiting
Lyon Cedex, 69373
-
France
Novartis Investigative Site
Active, not recruiting
Marseille, 13273
-
France
Novartis Investigative Site
Active, not recruiting
Paris Cedex 10, 75475
-
France
Novartis Investigative Site
Active, not recruiting
Vandoeuvre les Nancy, 54511
-
France
Germany
Novartis Investigative Site
Active, not recruiting
Mannheim, 68305
Baden-Wuerttemberg
Germany
Novartis Investigative Site
Active, not recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Withdrawn
Bonn, 53105
-
Germany
Novartis Investigative Site
Withdrawn
Dresden, 01307
-
Germany
Novartis Investigative Site
Completed
Duesseldorf, 40225
-
Germany
Novartis Investigative Site
Withdrawn
Essen, 45147
-
Germany
Novartis Investigative Site
Active, not recruiting
Frankfurt, 60590
-
Germany
Novartis Investigative Site
Withdrawn
Hamburg, 20099
-
Germany
Novartis Investigative Site
Withdrawn
Hannover, 30625
-
Germany
Novartis Investigative Site
Active, not recruiting
Heidelberg, 69120
-
Germany
Novartis Investigative Site
Active, not recruiting
Jena, 07740
-
Germany
Novartis Investigative Site
Active, not recruiting
Kiel, 24116
-
Germany
Novartis Investigative Site
Withdrawn
Leipzig, 04103
-
Germany
Novartis Investigative Site
Withdrawn
Muenchen, 81675
-
Germany
Novartis Investigative Site
Withdrawn
Nuernberg, 90419
-
Germany
Novartis Investigative Site
Withdrawn
Wuerzburg, 97080
-
Germany
Hungary
Novartis Investigative Site
Withdrawn
Budapest, 1085
-
Hungary
Novartis Investigative Site
Completed
Budapest, 1097
-
Hungary
Novartis Investigative Site
Active, not recruiting
Debrecen, 4032
-
Hungary
Novartis Investigative Site
Withdrawn
Kaposvar, 7400
-
Hungary
Israel
Novartis Investigative Site
Withdrawn
Haifa, 3525408
-
Israel
Novartis Investigative Site
Active, not recruiting
Jerusalem, 91120
-
Israel
Novartis Investigative Site
Active, not recruiting
Zrifin, 70300
-
Israel
Italy
Novartis Investigative Site
Completed
Bari, 70124
BA
Italy
Novartis Investigative Site
Withdrawn
Bologna, 40138
BO
Italy
Novartis Investigative Site
Withdrawn
Catania, 95123
CT
Italy
Novartis Investigative Site
Completed
Milano, 20122
MI
Italy
Novartis Investigative Site
Withdrawn
Milano, 20162
MI
Italy
Novartis Investigative Site
Withdrawn
Roma, 00161
RM
Italy
Novartis Investigative Site
Active, not recruiting
Napoli, 80132
-
Italy
Japan
Novartis Investigative Site
Active, not recruiting
Nagoya, 453-8511
Aichi
Japan
Novartis Investigative Site
Active, not recruiting
Toyoake city, 470 1192
Aichi
Japan
Novartis Investigative Site
Active, not recruiting
Kashiwa, 277 8577
Chiba
Japan
Novartis Investigative Site
Withdrawn
Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
Withdrawn
Sapporo city, 060 8648
Hokkaido
Japan
Novartis Investigative Site
Active, not recruiting
Kobe-shi, 650-0017
Hyogo
Japan
Novartis Investigative Site
Withdrawn
Yokohama city, 232 0024
Kanagawa
Japan
Novartis Investigative Site
Active, not recruiting
Osaka Sayama, 589 8511
Osaka
Japan
Novartis Investigative Site
Active, not recruiting
Suita city, 565 0871
Osaka
Japan
Novartis Investigative Site
Active, not recruiting
Bunkyo ku, 113-8677
Tokyo
Japan
Novartis Investigative Site
Active, not recruiting
Chuo-city, 409-3898
Yamanashi
Japan
Novartis Investigative Site
Active, not recruiting
Akita, 010-8543
-
Japan
Novartis Investigative Site
Active, not recruiting
Aomori, 030 8553
-
Japan
Novartis Investigative Site
Withdrawn
Osaka, 545-8586
-
Japan
Korea, Republic of
Novartis Investigative Site
Active, not recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Active, not recruiting
Busan, 49201
-
Korea, Republic of
Novartis Investigative Site
Active, not recruiting
Jeollanam-do, 519763
-
Korea, Republic of
Lebanon
Novartis Investigative Site
Completed
Ashrafieh, 166830
-
Lebanon
Novartis Investigative Site
Active, not recruiting
Beirut, 1107 2020
-
Lebanon
Novartis Investigative Site
Withdrawn
Beirut, 1136044
-
Lebanon
Mexico
Novartis Investigative Site
Active, not recruiting
Monterrey, 64460
Nuevo Leon
Mexico
Netherlands
Novartis Investigative Site
Active, not recruiting
Amsterdam, 1081 HV
-
Netherlands
Novartis Investigative Site
Active, not recruiting
Dordrecht, 3318AT
-
Netherlands
Romania
Novartis Investigative Site
Withdrawn
Bucharest, 022328
District 2
Romania
Novartis Investigative Site
Recruiting
Bucharest, 030171
-
Romania
Novartis Investigative Site
Completed
Cluj-Napoca, 400124
-
Romania
Novartis Investigative Site
Withdrawn
Craiova, 200136
-
Romania
Novartis Investigative Site
Active, not recruiting
Timisoara, 300079
-
Romania
Russian Federation
Novartis Investigative Site
Active, not recruiting
Moscow, 125167
-
Russian Federation
Novartis Investigative Site
Active, not recruiting
Moscow, 125284
-
Russian Federation
Novartis Investigative Site
Active, not recruiting
Saint Petersburg, 191024
-
Russian Federation
Novartis Investigative Site
Active, not recruiting
Saint Petersburg, 197341
-
Russian Federation
Saudi Arabia
Novartis Investigative Site
Active, not recruiting
Riyadh, 11211
-
Saudi Arabia
Serbia
Novartis Investigative Site
Active, not recruiting
Belgrade, 11000
-
Serbia
Novartis Investigative Site
Active, not recruiting
Novi Sad,
-
Serbia
Spain
Novartis Investigative Site
Withdrawn
Malaga, 29010
Andalucia
Spain
Novartis Investigative Site
Active, not recruiting
Bilbao, 48013
Bizkaia
Spain
Novartis Investigative Site
Active, not recruiting
Toledo, 45071
Castilla La Mancha
Spain
Novartis Investigative Site
Active, not recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Active, not recruiting
Hospitalet de LLobregat, 08907
Catalunya
Spain
Novartis Investigative Site
Withdrawn
Madrid, 28006
-
Spain
Novartis Investigative Site
Active, not recruiting
Madrid, 28034
-
Spain
Switzerland
Novartis Investigative Site
Active, not recruiting
Zürich, 8091
-
Switzerland
Turkey
Novartis Investigative Site
Active, not recruiting
Istanbul, 34098
TUR
Turkey
Novartis Investigative Site
Active, not recruiting
Adana, 01330
-
Turkey
Novartis Investigative Site
Active, not recruiting
Istanbul, 34093
-
Turkey
Novartis Investigative Site
Active, not recruiting
Izmir, 35040
-
Turkey
Novartis Investigative Site
Active, not recruiting
Samsun, 55139
-
Turkey
United Kingdom
Novartis Investigative Site
Active, not recruiting
Wirral, CH63 4JY
Merseyside
United Kingdom
Novartis Investigative Site
Active, not recruiting
Glasgow, G12 0YN
Scotland
United Kingdom
Novartis Investigative Site
Completed
Cardiff, CF4 4XN
-
United Kingdom
Novartis Investigative Site
Active, not recruiting
London, W12 0HS
-
United Kingdom
Novartis Investigative Site
Active, not recruiting
Oxford, OX3 7LJ
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111

Have a question?

Call 1-999-669-6682 or email [email protected]