Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    Abl001 | Russia
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03106779
Recruitment Status : Active, not recruiting
First Posted : April 10, 2017
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

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 or disease Intervention/treatment Phase
Chronic Myelogenous Leukemia Drug: ABL001 Drug: Bosutinib Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : October 26, 2017
Estimated Primary Completion Date : October 6, 2021
Estimated Study Completion Date : January 15, 2025


Arm Intervention/treatment
Experimental: ABL001
patients will be treated with ABL001
Drug: ABL001
40 mg tablets will be taken orally twice a day (BID)
Other Name: asciminib

Active Comparator: Bosutinib
patients will be treated with bosutinib
Drug: Bosutinib
500 mg tablets will be taken orally once daily (QD)




Primary Outcome Measures :
  1. Major Molecular Response (MMR) rate [ Time Frame: at 24 weeks ]
    To compare the MMR rate of ABL001 versus bosutinib


Secondary Outcome Measures :
  1. Major Molecular Response (MMR) rate [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  2. Complete Cytogenetic response rate [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib. Cytogenic response will include Complete, Partial, Major, Minor, Minimal and no response.

  3. Time to MMR [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  4. Duration of MMR [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  5. Time to CCyR [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  6. Duration of CCyR [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  7. Time to treatment failure [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  8. Progression free survival [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  9. Overall survival [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To compare additional parameters of the efficacy of ABL001 versus bosutinib

  10. Trough plasma concentrations [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To characterize the PK of ABL001 in the CML-CP population

  11. PK parameter: Cmax, [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To characterize the PK of ABL001 in the CML-CP population

  12. PK parameter: Tmax [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To characterize the PK of ABL001 in the CML-CP population

  13. PK parameter: AUC0-12h [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To characterize the PK of ABL001 in the CML-CP population

  14. PK parameter: CL/F [ Time Frame: 96 weeks after the last patient received the first study dose ]
    To characterize the PK of ABL001 in the CML-CP population



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03106779


Locations
Hide Hide 87 study locations
Layout table for location information
United States, Illinois
University of Chicago Hospital
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana Blood and Marrow Institute Regulatory - 2
Beech Grove, Indiana, United States, 46107
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Dana Farber Cancer Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Clinical Trials Office Main Site
Ann Arbor, Michigan, United States, 48109
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Weill Cornell Medicine NewYork Presbyterian Hospital
New York, New York, United States, 10021
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Utah Huntsman Cancer Center
Salt Lake City, Utah, United States, 84112
Argentina
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1221ADH
Novartis Investigative Site
Capital Federal, Argentina, C1114AAN
Novartis Investigative Site
Cordoba, Argentina, X5016KEH
Australia, South Australia
Novartis Investigative Site
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Novartis Investigative Site
Melbourne, Victoria, Australia, 3000
Australia, Western Australia
Novartis Investigative Site
Murdoch, Western Australia, Australia, 6150
Brazil
Novartis Investigative Site
Rio de Janeiro, RJ, Brazil, 20.211-030
Novartis Investigative Site
Sao Paulo, SP, Brazil, 05403 000
Novartis Investigative Site
Sao Paulo, SP, Brazil, 08270-070
Novartis Investigative Site
Porto Alegre, Brazil, 90035-003
Bulgaria
Novartis Investigative Site
Plovdiv, Bulgaria, 4002
Novartis Investigative Site
Varna, Bulgaria, 9000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Czechia
Novartis Investigative Site
Ostrava Poruba, Czech Republic, Czechia, 708 52
Novartis Investigative Site
Brno Bohunice, Czechia, 625 00
France
Novartis Investigative Site
Bordeaux, France, 33076
Novartis Investigative Site
Lyon Cedex, France, 69373
Novartis Investigative Site
Marseille, France, 13273
Novartis Investigative Site
Paris Cedex 10, France, 75475
Novartis Investigative Site
Vandoeuvre les Nancy, France, 54511
Germany
Novartis Investigative Site
Mannheim, Baden-Wuerttemberg, Germany, 68305
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Duesseldorf, Germany, 40225
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Jena, Germany, 07740
Novartis Investigative Site
Kiel, Germany, 24116
Hungary
Novartis Investigative Site
Budapest, Hungary, 1097
Novartis Investigative Site
Debrecen, Hungary, 4032
Israel
Novartis Investigative Site
Jerusalem, Israel, 91120
Novartis Investigative Site
Zrifin, Israel, 70300
Italy
Novartis Investigative Site
Bari, BA, Italy, 70124
Novartis Investigative Site
Milano, MI, Italy, 20122
Novartis Investigative Site
Napoli, Italy, 80132
Japan
Novartis Investigative Site
Nagoya, Aichi, Japan, 453-8511
Novartis Investigative Site
Toyoake city, Aichi, Japan, 470 1192
Novartis Investigative Site
Kashiwa, Chiba, Japan, 277 8577
Novartis Investigative Site
Kobe-shi, Hyogo, Japan, 650-0017
Novartis Investigative Site
Osaka Sayama, Osaka, Japan, 589 8511
Novartis Investigative Site
Suita city, Osaka, Japan, 565 0871
Novartis Investigative Site
Bunkyo ku, Tokyo, Japan, 113-8677
Novartis Investigative Site
Chuo-city, Yamanashi, Japan, 409-3898
Novartis Investigative Site
Akita, Japan, 010-8543
Novartis Investigative Site
Aomori, Japan, 030 8553
Korea, Republic of
Novartis Investigative Site
Seoul, Seocho Gu, Korea, Republic of, 06591
Novartis Investigative Site
Busan, Korea, Republic of, 49201
Novartis Investigative Site
Jeollanam-do, Korea, Republic of, 519763
Lebanon
Novartis Investigative Site
Ashrafieh, Lebanon, 166830
Novartis Investigative Site
Beirut, Lebanon, 1107 2020
Mexico
Novartis Investigative Site
Monterrey, Nuevo Leon, Mexico, 64460
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1081 HV
Novartis Investigative Site
Dordrecht, Netherlands, 3318AT
Romania
Novartis Investigative Site
Cluj-Napoca, Romania, 400124
Novartis Investigative Site
Timisoara, Romania, 300079
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 125167
Novartis Investigative Site
Moscow, Russian Federation, 125284
Novartis Investigative Site
Saint Petersburg, Russian Federation, 191024
Novartis Investigative Site
Saint Petersburg, Russian Federation, 197341
Saudi Arabia
Novartis Investigative Site
Riyadh, Saudi Arabia, 11211
Serbia
Novartis Investigative Site
Belgrade, Serbia, 11000
Novartis Investigative Site
Novi Sad, Serbia
Spain
Novartis Investigative Site
Bilbao, Bizkaia, Spain, 48013
Novartis Investigative Site
Toledo, Castilla La Mancha, Spain, 45071
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site
Madrid, Spain, 28034
Switzerland
Novartis Investigative Site
Zürich, Switzerland, 8091
Turkey
Novartis Investigative Site
Istanbul, TUR, Turkey, 34098
Novartis Investigative Site
Adana, Turkey, 01330
Novartis Investigative Site
Istanbul, Turkey, 34093
Novartis Investigative Site
Izmir, Turkey, 35040
Novartis Investigative Site
Samsun, Turkey, 55139
United Kingdom
Novartis Investigative Site
Wirral, Merseyside, United Kingdom, CH63 4JY
Novartis Investigative Site
Glasgow, Scotland, United Kingdom, G12 0YN
Novartis Investigative Site
Cardiff, United Kingdom, CF4 4XN
Novartis Investigative Site
London, United Kingdom, W12 0HS
Novartis Investigative Site
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03106779    
Other Study ID Numbers: CABL001A2301
First Posted: April 10, 2017    Key Record Dates
Last Update Posted: January 25, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ABL001
Phase 3
Chronic Myelogenous Leukemia
CML
bosutinib
tyrosine kinase inhibitor
Chronic myelogenous leukemia (CML)
chronic myeloid leukemia (CML)
chronic myelocytic leukemia (CML)
chronic granulocytic leukemia (CGL)
cancer of the white blood cells
clonal bone marrow stem cell disorder
proliferation of mature granulocytes
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases