Study Description
The study is designed to compare the tolerability of asciminib versus nilotinib for the treatment of newly diagnosed, previously untreated patients with Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).
This study is a phase IIIb, multi-center, open-label, randomized study of oral asciminib 80 mg once daily (QD) versus nilotinib 300 mg twice daily (BID) in adult patients with newly diagnosed Ph+ CML-CP.
Participants will be randomized in the study in a 1:1 ratio to asciminib or nilotinib. No crossover of study treatment across arms will be allowed.
Participants will be treated until unacceptable toxicity, disease progression and/or at the discretion of the investigator or the participants. A safety follow up visit/call will be performed approximately 30 days after end of treatment visit. Participants who discontinue study treatment prematurely due to any reason, will be followed up for survival and progression (to Accelerated Phase (AP)/Blast Crisis (BC)) up until end of study.
Interventions
Asciminib
Nilotinib
Eligibility Criteria
Inclusion Criteria:
Patients with CML-CP within 3 months of diagnosis.
Diagnosis of CML-CP (ELN 2020 criteria) with cytogenetic confirmation of the Philadelphia chromosome
Documented chronic phase CML will meet all the below criteria Baccarani et al 2013:
< 15% blasts in peripheral blood and bone marrow,
< 30% blasts plus promyelocytes in peripheral blood and bone marrow,
< 20% basophils in the peripheral blood,
PLT count ≥ 100 x 10^9/L (≥ 100,000/mm3), except treatment induced thrombocytopenia
No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly.
Evidence of typical BCR::ABL1 transcript [e14a2 and/or e13a2] which is amenable to standardized RQ-PCR quantification by the central laboratory assessment.
ECOG performance status of 0 or 1.
Adequate end organ function as defined by:
Total bilirubin (TBL) < 3 x ULN; patients with Gilbert's syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN,
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.
Patients 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 within normal limits or corrected to within normal limits with supplements prior to randomization.
CrCl as calculated using Cockcroft-Gault formula. **Pseudohyperkaliemia in case of thrombocytosis is not an exclusion criterion.
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.
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 of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) within 6 months prior to starting study treatment.
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 ≥ 450 ms on the average of three serial baseline ECG (using the QTcF formula). If QTcF ≥ 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTcF.
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).
History of significant congenital or acquired bleeding disorder unrelated to cancer.
Major surgery within 4 weeks prior to study entry or patients 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.
Known history of chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab/anti HBc) will be performed at screening. If anti-HBc is positive, HBV-DNA evaluation will be carried out at screening. A patient having positive HBV-DNA will not be enrolled in the study. Also, a patient with positive HBsAg will not be enrolled in the study. HCV Ab testing will also be performed at screening. For details on the criteria see Appendix 4.
History of Human Immunodeficiency Virus (HIV) unless well-controlled on a stable dose of anti-retroviral therapy at the time of screening.
Other protocol-defined Inclusion/exclusion criteria will apply.
Study Location
Novartis Investigative Site
Recruiting
Caba,Buenos Aires,C1181ACH,Argentina
Novartis Investigative Site
Recruiting
Caba,Buenos Aires,C1221ADH,Argentina
Novartis Investigative Site
Recruiting
Buenos aires,C1039AAC,Argentina
Novartis Investigative Site
Recruiting
Buenos Aires,C1114AAN,Argentina
Novartis Investigative Site
Recruiting
Buenos Aires,C1425AUM,Argentina
Novartis Investigative Site
Recruiting
Pleven,5800,Bulgaria
Novartis Investigative Site
Recruiting
Sofia,1413,Bulgaria
Novartis Investigative Site
Recruiting
Plovdiv,4002,Bulgaria
Novartis Investigative Site
Recruiting
Sofia,1431,Bulgaria
Novartis Investigative Site
Recruiting
Sofia,1797,Bulgaria
Novartis Investigative Site
Recruiting
Varna,9010,Bulgaria
Novartis Investigative Site
Recruiting
Toronto,Ontario,M5G 2M9,Canada
Novartis Investigative Site
Recruiting
Praha 10,100 34,Czech Republic
Novartis Investigative Site
Recruiting
Praha 2,Czech Republic,128 20,Czech Republic
Novartis Investigative Site
Recruiting
Brno Bohunice,Czech Republic,625 00,Czech Republic
Novartis Investigative Site
Recruiting
Plzen-Bory,30599,Czech Republic
Novartis Investigative Site
Recruiting
Toulouse,31059,France
Novartis Investigative Site
Recruiting
Nantes Cedex 1,44093,France
Novartis Investigative Site
Recruiting
Marseille,13273,France
Novartis Investigative Site
Recruiting
Strasbourg,67200,France
Novartis Investigative Site
Recruiting
Bordeaux,33076,France
Novartis Investigative Site
Recruiting
Nice,06202,France
Novartis Investigative Site
Recruiting
Lyon,69373,France
Novartis Investigative Site
Recruiting
Caen Cedex,14033,France
Novartis Investigative Site
Recruiting
Vandoeuvre les Nancy cedex,54511,France
Novartis Investigative Site
Recruiting
Paris 10,75475,France
Novartis Investigative Site
Recruiting
Lille,59037,France
Novartis Investigative Site
Recruiting
Poitiers,86000,France
Novartis Investigative Site
Recruiting
Clermont Ferrand,63003,France
Novartis Investigative Site
Recruiting
Tuebingen,72076,Germany
Novartis Investigative Site
Recruiting
Essen,45147,Germany
Novartis Investigative Site
Recruiting
Wuerzburg,97080,Germany
Novartis Investigative Site
Recruiting
Halle S,06120,Germany
Novartis Investigative Site
Recruiting
Augsburg,86179,Germany
Novartis Investigative Site
Recruiting
Frankfurt,60590,Germany
Novartis Investigative Site
Recruiting
Heidelberg,69120,Germany
Novartis Investigative Site
Recruiting
Luebeck,23538,Germany
Novartis Investigative Site
Recruiting
Hamburg,20246,Germany
Novartis Investigative Site
Recruiting
Bad Saarow,15526,Germany
Novartis Investigative Site
Recruiting
Ulm,89081,Germany
Novartis Investigative Site
Recruiting
Freiburg,79106,Germany
Novartis Investigative Site
Recruiting
Bremen,28177,Germany
Novartis Investigative Site
Recruiting
Hannover,30161,Germany
Novartis Investigative Site
Recruiting
Paderborn,33098,Germany
Novartis Investigative Site
Recruiting
Regensburg,93049,Germany
Novartis Investigative Site
Recruiting
Muenchen,Bayern,81241,Germany
Novartis Investigative Site
Recruiting
Dresden,Sachsen,01307,Germany
Novartis Investigative Site
Recruiting
Magdeburg,39104,Germany
Novartis Investigative Site
Recruiting
Chemnitz,09113,Germany
Novartis Investigative Site
Recruiting
Bayreuth,95445,Germany
Novartis Investigative Site
Recruiting
Leipzig,04103,Germany
Novartis Investigative Site
Recruiting
Muenchen,80377,Germany
Novartis Investigative Site
Recruiting
Mannheim,Baden Wuerttemberg,68305,Germany
Novartis Investigative Site
Recruiting
Berlin,13353,Germany
Novartis Investigative Site
Recruiting
Jena,07740,Germany
Novartis Investigative Site
Recruiting
Erlangen,91054,Germany
Novartis Investigative Site
Recruiting
Marburg,35039,Germany
Novartis Investigative Site
Recruiting
Aachen,52074,Germany
Novartis Investigative Site
Recruiting
Velbert,North Rhine-Westphalia,42551,Germany
Novartis Investigative Site
Recruiting
Bonn,53105,Germany
Novartis Investigative Site
Recruiting
Athens,115 27,Greece
Novartis Investigative Site
Recruiting
Thessaloniki,GR,570 10,Greece
Novartis Investigative Site
Recruiting
Ioannina,GR,455 00,Greece
Novartis Investigative Site
Recruiting
Larissa,GR,411 10,Greece
Novartis Investigative Site
Recruiting
Patras,265 00,Greece
Novartis Investigative Site
Recruiting
Athens,106 76,Greece
Novartis Investigative Site
Recruiting
Budapest,1085,Hungary
Novartis Investigative Site
Recruiting
Budapest,1097,Hungary
Novartis Investigative Site
Recruiting
Eger,3300,Hungary
Novartis Investigative Site
Recruiting
New Delhi,110029,India
Novartis Investigative Site
Recruiting
Ahmedabad,Gujrat,380009,India
Novartis Investigative Site
Recruiting
Varanasi,Uttar Pradesh,221010,India
Novartis Investigative Site
Recruiting
Rishikesh,Uttarakhand,249203,India
Novartis Investigative Site
Recruiting
Chennai,Tamilnadu,600036,India
Novartis Investigative Site
Recruiting
Meldola,FC,47014,Italy
Novartis Investigative Site
Recruiting
Pisa,PI,56126,Italy
Novartis Investigative Site
Recruiting
Milano,MI,20162,Italy
Novartis Investigative Site
Recruiting
Bari,BA,70124,Italy
Novartis Investigative Site
Recruiting
Torino,TO,10126,Italy
Novartis Investigative Site
Recruiting
Amman,11941,Jordan
Novartis Investigative Site
Recruiting
Bundang Gu,Gyeonggi Do,13620,Korea, Republic of
Novartis Investigative Site
Recruiting
Uijeongbu si,Gyeonggi Do,11759,Korea, Republic of
Novartis Investigative Site
Recruiting
Petaling Jaya,Selangor Darul Ehsan,46150,Malaysia
Novartis Investigative Site
Recruiting
Kuala Lumpur,59100,Malaysia
Novartis Investigative Site
Recruiting
Kuching,Sarawak,93586,Malaysia
Novartis Investigative Site
Recruiting
Alor Setar,Kedah,05460,Malaysia
Novartis Investigative Site
Recruiting
Penang,10050,Malaysia
Novartis Investigative Site
Recruiting
Dordrecht,3318AT,Netherlands
Novartis Investigative Site
Recruiting
Muscat,123,Oman
Novartis Investigative Site
Recruiting
Bucuresti,021494,Romania
Novartis Investigative Site
Recruiting
Cluj-Napoca,400124,Romania
Novartis Investigative Site
Recruiting
Tg Mures,Mures,540136,Romania
Novartis Investigative Site
Recruiting
Craiova,200136,Romania
Novartis Investigative Site
Recruiting
Timisoara,300079,Romania
Novartis Investigative Site
Recruiting
Bucharest,District 2,022328,Romania
Novartis Investigative Site
Recruiting
Sibiu,550245,Romania
Novartis Investigative Site
Recruiting
Bucharest,030 171,Romania
Novartis Investigative Site
Recruiting
Singapore,169608,Singapore
Novartis Investigative Site
Recruiting
Singapore,S308433,Singapore
Novartis Investigative Site
Recruiting
Singapore,119228,Singapore
Novartis Investigative Site
Recruiting
Kosice,Slovak Republic,040 66,Slovakia
Novartis Investigative Site
Recruiting
Bratislava,85107,Slovakia
Novartis Investigative Site
Recruiting
Pretoria,0044,South Africa
Novartis Investigative Site
Recruiting
Soweto,Gauteng,2013,South Africa
Novartis Investigative Site
Recruiting
Genève,1211,Switzerland
Novartis Investigative Site
Recruiting
Istanbul,TUR,34098,Turkey
Novartis Investigative Site
Recruiting
Izmir,35040,Turkey
Novartis Investigative Site
Recruiting
Ankara,06100,Turkey
Novartis Investigative Site
Recruiting
Abu Dhabi,United Arab Emirates
Novartis Investigative Site
Recruiting
London,W12 0HS,United Kingdom
Novartis Investigative Site
Recruiting
Glasgow,G12 0YN,United Kingdom
Novartis Investigative Site
Recruiting
Gloucester,GL1 3NN,United Kingdom
Novartis Investigative Site
Recruiting
Truro,Cornwall,TR1 3LJ,United Kingdom
Novartis Investigative Site
Recruiting
London,SE5 9RS,United Kingdom
Novartis Investigative Site
Recruiting
Gwent,NP9 2UB,United Kingdom
Florida Cancer Specialists Pan .
Recruiting
Tallahassee,Lindsey Murkerson (615-329-7482) email: [email protected] -- Jeffrey Bubis,32308 - Florida,United States
Texas Oncology P A Midtown
Recruiting
Dallas,Shawnty Witham (512-421-4100) email: [email protected] -- Jason M Melear,75251 - Texas,United States
Hematology and Oncology Clinic .
Recruiting
Baton Rouge,Paige Pigee email: [email protected] -- Michael Castine III,70809 - Louisiana,United States
Texas Oncology P A .
Recruiting
Bedford,Virginia Butterworth email: [email protected] -- Andrew Jackson,76022 - Texas,United States
Oncology Hematology Care Inc .
Recruiting
Cincinnati,Zachary Beck email: [email protected] -- Kruti Patel,45242 - Ohio,United States
Illinois Cancer Care
Recruiting
Peoria,Heather Thulean (309-243-3661) email: [email protected] -- Srinivas Jujjavarapu,61615 - Illinois,United States
Virginia Oncology Associates VOA - Princess Anne
Recruiting
Norfolk,Emily Jones (757-368-0437) email: [email protected] -- Celeste Bremer,23502 - Virginia,United States
Regions Hospital Oncology Research Consortium
Recruiting
Saint Paul,Yan Ji,55101 - Minnesota,United States
Lumi Research
Recruiting
Kingwood,Whitney Nwole (281-809-0676) email: [email protected] -- Saleha Sajid,77339 - Texas,United States
Williamette Cancer Center
Recruiting
Eugene,Alexandra Chavez email: [email protected] -- Luke Fletcher,97401 - Oregon,United States
Rocky Mountain Cancer Centers USOR
Recruiting
Boulder,Lee Dimopoulos (303-385-2000) email: [email protected] -- David J Andorsky,80304 - Colorado,United States
Messino Cancer Centers
Recruiting
Asheville,Taylor McNeely email: [email protected] -- Andrew Beardsley,28806 - North Carolina,United States
Arizona Oncology Associates .
Recruiting
Phoenix,Alan Langerak,85016 - Arizona,United States
Sarah Cannon Research Institute HCA Healthcare Research Inst
Recruiting
Nashville,Vanesa Veletanlic (615-515-1900) email: [email protected] -- Stephen Strickland,37203 - Tennessee,United States
Minnesota Oncology Hematology P A Minnesota Oncology Hematology
Recruiting
Minneapolis,Brianna Lennox (612-884-6300) email: [email protected] -- Danielle Tippit,55404 - Minnesota,United States
Florida Cancer Specialists Dept of Oncology (2)
Recruiting
Fort Myers,Kelly Whitehead (+1 727 216 1143) email: [email protected] -- Adewale Alade Fawole,33901 - Florida,United States
Worldwide Contacts
If the location of your choosing does not feature any contact detail, please reach out using the information below.