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: Nov 14, 2022

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 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 
Dec 05, 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.
Participants with CML-CP within 3 months of diagnosis.
Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of Philadelphia chromosome

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 (CrCl) ≥ 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. Participants must have the following laboratory values within normal limits 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 CrCl* ≥ 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 CrCl* ≥ 90 mL/min)
Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl* ≥ 90 mL/min)
For patients with mild to moderate renal impairment (CrCl* ≥ 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.

*CrCl 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 either imatinib, or nilotinib, or dasatinib or bosutinib for ≤2 weeks is allowed, but no other treatment with other tyrosine kinase inhibitors prior to randomization 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 ms (male patients), ≥460 ms (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF ≥ 450 ms 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
City of Hope National Medical Center
Recruiting
Duarte, 91010 - California
Contact: (+1 626 256 4673 Ext 85013) Paul Koller
United States
UCLA Medical Center
Recruiting
Los Angeles, 90095 - California
Contact: Laura H Yu - [email protected] - Gary Schiller
United States
Rocky Mountain Cancer Centers
Recruiting
Longmont, 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: Melissa Staggs (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: Sheila Gagne (615-329-7482) - [email protected] - 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
University of Chicago
Recruiting
Chicago, 60637 - Illinois
Contact: Anielska Brautigam (773-702-8582) - [email protected] - Richard A. Larson
United States
Illinois Cancer Care P.C. IL Cancer Specialists
Recruiting
Peoria, 61615-7828 - Illinois
Contact: Anginique Walker (847-827-0319) - [email protected] - Leonard Klein
United States
University of Iowa Hospitals and Clinics Univ of Iowa Hosp & Clinic
Recruiting
Iowa City, 52242 - Iowa
Contact: (319-356-3425) Grerk Sutamtewagul
United States
University of Kentucky
Recruiting
Lexington, 40536 - Kentucky
Contact: (859-218-5151) Reinhold Munker
United States
University of Massachusetts Medical Center Dept of Oncology
Recruiting
Worcester, 01655 - Massachusetts
Contact: (774-443-7433) Jonathan Gerber
United States
University of Michigan Clinical Trials Office
Recruiting
Ann Arbor, 48109 - Michigan
Contact: D Andra Featherstone (734-647-8925) - [email protected] - Moshe Talpaz
United States
Wake Forest University Baptist Medical Center Comprehensive Cancer Ctr
Recruiting
Winston-Salem, 27157 - North Carolina
Contact: (336-716-4464) Bayard L. Powell
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: Julie Morehouse - [email protected] - Moshe Levy
United States
Texas Oncology
Recruiting
Dallas, 75246 - Texas
Contact: (+1 915 599 1313) Praveen Kumar Tumula
United States
Texas Oncology P A Austin
Recruiting
Dallas, 75251 - Texas
Contact: Francisca Fernandez (512-421-4163) - [email protected] - Jason M Melear
United States
University of TX MD Anderson Cancer Center
Recruiting
Houston, 77030 - Texas
Contact: Allison Pike (713-745-1936) - [email protected] - Ghayas C Issa
United States
Lumi Research
Recruiting
Kingwood, 77339 - Texas
Contact: (281-809-0676) Saleha Sajid
United States
Texas Oncology Northeast Texas
Recruiting
Tyler, 75702 - Texas
Contact: Karen Wollard (903-579-9867) - [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
Recruiting
Kingswood, 2747
New South Wales
Australia
Novartis Investigative Site
Recruiting
Port Macquarie, 2444
New South Wales
Australia
Novartis Investigative Site
Recruiting
Woolloongabba, 4102
Queensland
Australia
Novartis Investigative Site
Recruiting
Adelaide, 5000
South Australia
Australia
Novartis Investigative Site
Recruiting
SouthPort, 4215
-
Australia
Austria
Novartis Investigative Site
Recruiting
Linz, 4010
Upper Austria
Austria
Novartis Investigative Site
Recruiting
Wien, 1090
-
Austria
Belgium
Novartis Investigative Site
Recruiting
Bruxelles, 1000
-
Belgium
Novartis Investigative Site
Recruiting
Hasselt, 3500
-
Belgium
Novartis Investigative Site
Recruiting
Leuven, 3000
-
Belgium
Bulgaria
Novartis Investigative Site
Recruiting
Sofia, 1797
-
Bulgaria
Novartis Investigative Site
Recruiting
Varna, 9010
-
Bulgaria
Canada
Novartis Investigative Site
Recruiting
Calgary, T2N 4N2
Alberta
Canada
Novartis Investigative Site
Recruiting
Hamilton, L8V 1C3
Ontario
Canada
Novartis Investigative Site
Recruiting
Ottawa, K1H 8L6
Ontario
Canada
Novartis Investigative Site
Recruiting
Toronto, M5G 2M9
Ontario
Canada
China
Novartis Investigative Site
Recruiting
Hefei, 230001
Anhui
China
Novartis Investigative Site
Recruiting
Chongqing, 400016
Chongqing
China
Novartis Investigative Site
Recruiting
Guangzhou, 510515
Guangdong
China
Novartis Investigative Site
Recruiting
Shenzhen, 518037
Guangdong
China
Novartis Investigative Site
Recruiting
Zhengzhou, 450008
Henan
China
Novartis Investigative Site
Recruiting
Wuhan, 430022
Hubei
China
Novartis Investigative Site
Recruiting
Chifeng, 024099
Inner Mongolia
China
Novartis Investigative Site
Recruiting
Nanjing,
Jiangsu
China
Novartis Investigative Site
Recruiting
Nantong, 226000
Jiangsu
China
Novartis Investigative Site
Recruiting
Suzhou, 215006
Jiangsu
China
Novartis Investigative Site
Recruiting
Taiyuan, 030001
Shanxi
China
Novartis Investigative Site
Recruiting
Xian, 710068
Shanxi
China
Novartis Investigative Site
Recruiting
Chengdu, 610041
Sichuan
China
Novartis Investigative Site
Recruiting
Tianjin, 300020
Tianjin
China
Novartis Investigative Site
Recruiting
Hangzhou, 310003
Zhejiang
China
Novartis Investigative Site
Recruiting
Wenzhou, 325000
Zhejiang
China
Novartis Investigative Site
Recruiting
Beijing, 100044
-
China
Novartis Investigative Site
Recruiting
Beijing, 100730
-
China
Novartis Investigative Site
Recruiting
Lanzhou,
-
China
Novartis Investigative Site
Recruiting
Shanghai, 200025
-
China
Czech Republic
Novartis Investigative Site
Recruiting
Brno Bohunice, 625 00
Czech Republic
Czech Republic
Novartis Investigative Site
Recruiting
Hradec Kralove, 500 05
CZE
Czech Republic
Novartis Investigative Site
Recruiting
Ostrava, 708 52
Poruba
Czech Republic
Denmark
Novartis Investigative Site
Recruiting
Aarhus, 8000
-
Denmark
Novartis Investigative Site
Recruiting
Copenhagen, DK-2100
-
Denmark
Novartis Investigative Site
Recruiting
Roskilde, 4000
-
Denmark
Finland
Novartis Investigative Site
Recruiting
Helsinki, FIN 00290
-
Finland
Novartis Investigative Site
Recruiting
Turku, 20520
-
Finland
France
Novartis Investigative Site
Recruiting
Bordeaux, 33076
-
France
Novartis Investigative Site
Recruiting
Lyon Cedex, 69373
-
France
Novartis Investigative Site
Recruiting
Nantes Cedex 1, 44093
-
France
Novartis Investigative Site
Recruiting
Paris Cedex 10, 75475
-
France
Germany
Novartis Investigative Site
Recruiting
Mannheim, 68305
Baden-Wuerttemberg
Germany
Novartis Investigative Site
Recruiting
Aachen, 52074
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Recruiting
Frankfurt, 60590
-
Germany
Novartis Investigative Site
Recruiting
Jena, 07740
-
Germany
Novartis Investigative Site
Recruiting
Luebeck, 23538
-
Germany
Hungary
Novartis Investigative Site
Recruiting
Debrecen, 4032
-
Hungary
Novartis Investigative Site
Recruiting
Kaposvar, 7400
-
Hungary
Novartis Investigative Site
Recruiting
Kecskemet, 6001
-
Hungary
India
Novartis Investigative Site
Recruiting
Kolkata, 700160
West Bengal
India
Novartis Investigative Site
Recruiting
Delhi, 110 085
-
India
Israel
Novartis Investigative Site
Recruiting
Petah Tikva,
-
Israel
Novartis Investigative Site
Recruiting
Ramat Gan, 52621
-
Israel
Novartis Investigative Site
Recruiting
Tel Aviv, 6423906
-
Israel
Italy
Novartis Investigative Site
Recruiting
Bologna, 40138
BO
Italy
Novartis Investigative Site
Recruiting
Milano, 20122
MI
Italy
Novartis Investigative Site
Recruiting
Reggio Emilia, 42123
RE
Italy
Novartis Investigative Site
Recruiting
Roma, 00161
RM
Italy
Novartis Investigative Site
Recruiting
Verona, 37126
VR
Italy
Japan
Novartis Investigative Site
Recruiting
Nagoya, 453-8511
Aichi
Japan
Novartis Investigative Site
Recruiting
Toyoake city, 470 1192
Aichi
Japan
Novartis Investigative Site
Recruiting
Kashiwa, 277 8577
Chiba
Japan
Novartis Investigative Site
Recruiting
Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
Recruiting
Fukushima city, 960 1295
Fukushima
Japan
Novartis Investigative Site
Recruiting
Sapporo city, 060 8648
Hokkaido
Japan
Novartis Investigative Site
Recruiting
Kobe-city, 650-0047
Hyogo
Japan
Novartis Investigative Site
Recruiting
Kurashiki-city, 710-8602
Okayama
Japan
Novartis Investigative Site
Recruiting
Osaka Sayama, 589 8511
Osaka
Japan
Novartis Investigative Site
Recruiting
Suita, 565 0871
Osaka
Japan
Novartis Investigative Site
Recruiting
Sunto Gun, 411 8777
Shizuoka
Japan
Novartis Investigative Site
Recruiting
Shimotsuke, 329-0498
Tochigi
Japan
Novartis Investigative Site
Recruiting
Chuo-city, 409-3898
Yamanashi
Japan
Novartis Investigative Site
Recruiting
Akita, 010-8543
-
Japan
Novartis Investigative Site
Recruiting
Osaka, 545-8586
-
Japan
Novartis Investigative Site
Recruiting
Yamagata, 990 9585
-
Japan
Korea, Republic of
Novartis Investigative Site
Recruiting
Uijeongbu si, 11759
Gyeonggi Do
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03722
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 06351
-
Korea, Republic of
Malaysia
Novartis Investigative Site
Recruiting
Kuantan, 25100
Pahang
Malaysia
Novartis Investigative Site
Recruiting
Subang Jaya, 47500
Selangor
Malaysia
Novartis Investigative Site
Recruiting
Pulau Pinang, 10990
-
Malaysia
Novartis Investigative Site
Recruiting
Selangor, 68000
-
Malaysia
Netherlands
Novartis Investigative Site
Recruiting
Amsterdam, 1081 HV
-
Netherlands
Norway
Novartis Investigative Site
Recruiting
Bergen, 5021
-
Norway
Novartis Investigative Site
Recruiting
Oslo, 0372
-
Norway
Novartis Investigative Site
Recruiting
Trondheim, 7006
-
Norway
Portugal
Novartis Investigative Site
Recruiting
Lisboa, 1099 023
-
Portugal
Novartis Investigative Site
Recruiting
Porto, 4200-072
-
Portugal
Novartis Investigative Site
Recruiting
Vila Nova de Gaia, 4434 502
-
Portugal
Russian Federation
Novartis Investigative Site
Recruiting
Saint Petersburg, 191024
-
Russian Federation
Singapore
Novartis Investigative Site
Recruiting
Singapore, 119228
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 169608
-
Singapore
Slovakia
Novartis Investigative Site
Recruiting
Bratislava, 83310
Slovak Republic
Slovakia
Novartis Investigative Site
Recruiting
Kosice, 040 66
Slovak Republic
Slovakia
Spain
Novartis Investigative Site
Recruiting
Granada, 18014
Andalucia
Spain
Novartis Investigative Site
Recruiting
Badalona, 08916
Catalunya
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08036
Catalunya
Spain
Novartis Investigative Site
Recruiting
El Palmar, 30120
Murcia
Spain
Novartis Investigative Site
Recruiting
Pamplona, 31008
Navarra
Spain
Novartis Investigative Site
Recruiting
Madrid, 28046
-
Spain
Sweden
Novartis Investigative Site
Recruiting
Goteborg, 413 45
-
Sweden
Novartis Investigative Site
Recruiting
Lund, 221 85
-
Sweden
Novartis Investigative Site
Recruiting
Stockholm, 141 86
-
Sweden
Switzerland
Novartis Investigative Site
Recruiting
Bellinzona, 6850
-
Switzerland
Novartis Investigative Site
Recruiting
Zürich, 8091
-
Switzerland
Taiwan
Novartis Investigative Site
Recruiting
Kaohsiung City, 83301
-
Taiwan
Novartis Investigative Site
Recruiting
Taichung, 40447
-
Taiwan
United Kingdom
Novartis Investigative Site
Recruiting
London, W12 0NN
-
United Kingdom
Novartis Investigative Site
Recruiting
Nottingham, NG5
-
United Kingdom
Novartis Investigative Site
Recruiting
Oxford, OX3 7LJ
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]