A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP

A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase

ClinicalTrials.gov Identifier: NCT04971226

Novartis Reference Number: CABL001J12301

Last Update: May 11, 2022

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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 study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the following treatment options for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD.

Condition 
Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Oct 06, 2021
Completion date 
Nov 24, 2028
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Imatinib
Comes in 100 mg and 400 mg tablets and taken orally
Drug
Nilotinib
Comes in 150 mg capsules and taken orally
Drug
Bosutinib
Comes in 100 mg and 400 mg tablets and taken orally
Drug
Dasatinib
Comes in 70 mg and 100 mg tablets and taken orally
Drug
Asciminib
Comes in 40 mg tablets and taken orally

Eligibility Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

Male or female patients ≥ 18 years of age.
Patients with CML-CP within 3 months of diagnosis.
Diagnosis of CML-CP with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations (presence of BCR-ABL1 in a review of a minimum 20 metaphases is required).

Documented chronic phase CML will meet all the below criteria Hochhaus et al 2020:

< 15% blasts in peripheral blood and bone marrow,
< 30% blasts plus promyelocytes in peripheral blood and bone marrow,
< 20% basophils in the peripheral blood,
Platelet count ≥ 100 x 109/L (≥ 100,000/mm3),

No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0,or 1. 5. Adequate end organ function as defined by:

Total bilirubin < 3 x ULN; patients with Gilbert's syndrome may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
Creatinine clearance (ClCr) ≥ 30 mL/min as calculated using Cockcroft-Gault formula,
Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis 6. Patients must have the following laboratory values ≥ LLN or corrected to within normal limits with supplements prior to randomization:
Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with ClCr* ≥ 90 mL/min)
Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with ClCr* ≥ 90 mL/min)
Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with ClCr* ≥ 90 mL/min)
For patients with mild to moderate renal impairment (ClCr* ≥ 30 mL/min and <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be ≥ LLN or corrected to within normal limits with supplements prior to randomization.

*ClCr as calculated using Cockcroft-Gault formula 7. Ability to provide written informed consent prior to any study related screening procedures being performed.

8. Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which is amenable to standardized Real time quantitative polymerase chain reaction (RQ-PCR) quantification.

Exclusion Criteria:

Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide. Treatment with imatinib for ≤2 weeks is allowed, but no other treatment with tyrosine kinase inhibitors prior to study entry is permitted.
Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).

Impaired cardiac function or cardiac repolarization abnormality including but not limited to any one 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)
QTc ≥ 450 msec (male patients), ≥460 msec (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF ≥ 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
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; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia). Please refer to Section 6.3.1
History of significant congenital or acquired bleeding disorder unrelated to cancer.
Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery.
History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.

Other protocol-defined Inclusion/exclusion criteria will apply.

Study Locations

United States
Rocky Mountain Cancer Centers
Recruiting
Denver, 80501 - Colorado
Contact: Bobbie Donnachaidh - [email protected] - David J Andorsky
United States
Florida Cancer Specialists Dept of Oncology (2)
Recruiting
Fort Myers, 33901 - Florida
Contact: BJ Conklin (727-216-1143) - [email protected] - Vijay Patel
United States
Florida Cancer Specialists
Recruiting
Fort Myers, 33901 - Florida
Contact: David Langlois (239-274-9930) - [email protected] - Anjan J Patel
United States
Florida Cancer Specialists Panhandle
Recruiting
Tallahassee, 32308 - Florida
Contact: (615-329-7482) Pareshkumar Patel
United States
Florida Cancer Specialists
Recruiting
West Palm Beach, 33401 - Florida
Contact: Jennifer Demko (561-366-4149) - [email protected] - Shachar Peles
United States
Illinois Cancer Care P.C. IL Cancer Specialists
Recruiting
Peoria, 61615-7828 - Illinois
Contact: (847-827-0319) Leonard Klein
United States
University of Kentucky
Recruiting
Lexington, 40536 - Kentucky
Contact: (859-218-5151) Reinhold Munker
United States
Oncology Hematology Care Inc
Recruiting
Cincinnati, 45242 - Ohio
Contact: Maggie Lair - [email protected] - Edward R Broun
United States
Williamette Cancer Center
Recruiting
Eugene, 97401 - Oregon
Contact: Nichole Fischer - [email protected] - Luke Fletcher
United States
Avera Cancer Avera Cancer Institute
Recruiting
Sioux Falls, 57105 - South Dakota
Contact: Lauren Donelan (605-322-3291) - [email protected] - Roberto Ferro Valdes
United States
Chattanooga Oncology and Hematology Associates PC Tennessee Oncology Chattanooga
Recruiting
Chattanooga, 37404 - Tennessee
Contact: Kim Tucker (+1 423 698 1844) - [email protected] - Bertrand Marquess Anz
United States
Texas Oncology Texas Onc - Amarillo
Recruiting
Dallas, 75246 - Texas
Contact: Tanya Jauch-Worley (+1 806 358 8654) - [email protected] - Praveen Kumar Tumula
United States
Texas Oncology-Baylor USO
Recruiting
Dallas, 75246 - Texas
Contact: Jessica Fagala - [email protected] - Moshe Levy
United States
Texas Oncology P A Austin
Recruiting
Dallas, 75251 - Texas
Contact: Francisca Fernandez (512-421-4163) - [email protected] - Jason M Melear
United States
US Oncology P A
Recruiting
Tyler, 75702 - Texas
Contact: Penny Watkins (903-579-9800) - [email protected] - Habte Yimer
United States
Virginia Cancer Specialists
Recruiting
Gainesville, 20155 - Virginia
Contact: Marcy Sullivan - [email protected] - Mitul Gandhi
United States
Virginia Oncology Associates
Recruiting
Norfolk, 23502 - Virginia
Contact: Tamira Mann (757-466-8683) - [email protected] - Celeste Bremer
United States
Australia
Novartis Investigative Site
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Kingswood, 2747
New South Wales
Australia
Novartis Investigative Site
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Port Macquarie, 2444
New South Wales
Australia
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Woolloongabba, 4102
Queensland
Australia
Austria
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Linz, 4010
Upper Austria
Austria
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Wien, 1090
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Austria
Belgium
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Leuven, 3000
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Belgium
Canada
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Hamilton, L8V 1C3
Ontario
Canada
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Ottawa, K1H 8L6
Ontario
Canada
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Toronto, M5G 2M9
Ontario
Canada
China
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Guangzhou, 510515
Guangdong
China
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Shenzhen, 518037
Guangdong
China
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Wuhan, 430022
Hubei
China
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Nantong, 226000
Jiangsu
China
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Chengdu, 610041
Sichuan
China
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Tianjin, 300020
Tianjin
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Czech Republic
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Brno Bohunice, 625 00
Czech Republic
Czech Republic
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Ostrava Poruba, 708 52
Czech Republic
Czech Republic
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Hradec Kralove, 500 05
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Czech Republic
Denmark
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Aarhus, 8000
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Finland
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Helsinki, FIN 00290
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France
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Bordeaux, 33076
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France
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Lyon Cedex, 69373
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France
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Nantes Cedex 1, 44093
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France
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Paris Cedex 10, 75475
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France
Germany
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Mannheim, 68305
Baden-Wuerttemberg
Germany
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Aachen, 52074
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Germany
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Berlin, 13353
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Germany
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Frankfurt, 60590
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Germany
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Jena, 07740
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Germany
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Luebeck, 23538
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Germany
Hungary
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Debrecen, 4032
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Hungary
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Kaposvar, 7400
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Hungary
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Kecskemet, 6001
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Hungary
India
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Delhi, 110 085
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Israel
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Petah Tikva,
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Israel
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Ramat Gan, 52621
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Israel
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Tel Aviv, 6423906
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Israel
Italy
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Bologna, 40138
BO
Italy
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Verona, 37126
VR
Italy
Japan
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Toyoake city, 470 1192
Aichi
Japan
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Fukushima city, 960 1295
Fukushima
Japan
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Suita city, 565 0871
Osaka
Japan
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Sunto Gun, 411 8777
Shizuoka
Japan
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Shimotsuke, 329-0498
Tochigi
Japan
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Akita, 010-8543
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Japan
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Yamagata, 990 9585
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Japan
Korea, Republic of
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Uijeongbu si, 11759
Gyeonggi Do
Korea, Republic of
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Seoul, 06591
Seocho Gu
Korea, Republic of
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Seoul, 03080
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Korea, Republic of
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Seoul, 03722
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Korea, Republic of
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Seoul, 06351
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Korea, Republic of
Malaysia
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Kuantan, 25100
Pahang
Malaysia
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Subang Jaya, 47500
Selangor
Malaysia
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Pulau Pinang, 10990
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Malaysia
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Selangor, 68000
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Malaysia
Norway
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Bergen, 5021
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Norway
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Oslo, 0372
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Norway
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Trondheim, 7006
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Norway
Russian Federation
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Saint Petersburg, 191024
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Russian Federation
Singapore
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Singapore, 119228
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Singapore
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Singapore, 169608
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Singapore
Slovakia
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Bratislava, 83310
Slovak Republic
Slovakia
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Kosice, 040 66
Slovak Republic
Slovakia
Spain
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Granada, 18014
Andalucia
Spain
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Barcelona, 08036
Catalunya
Spain
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El Palmar, 30120
Murcia
Spain
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Pamplona, 31008
Navarra
Spain
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Madrid, 28046
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Spain
Sweden
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Goteborg, 413 45
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Sweden
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Stockholm, 141 86
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Sweden
Switzerland
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Bellinzona, 6850
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Switzerland
Taiwan
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Taichung, 40447
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Taiwan
United Kingdom
Novartis Investigative Site
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London, W12 0NN
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United Kingdom

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Phone: 
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