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CTRI Number  CTRI/2023/07/054677 [Registered on: 03/07/2023] Trial Registered Prospectively
Last Modified On: 12/01/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   A study to investigate the effect of asciminib versus nilotinib in adult patients with Leukemia 
Scientific Title of Study   A phase IIIb, multi-center, open-label, randomized study of tolerability and efficacy of oral asciminib versus nilotinib in patients with newly diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
CABL001J12302 Protocol Version 00.00 dated 24 May 2022  Protocol Number 
NCT05456191  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Murugananthan K 
Designation  SSO Country Head 
Affiliation  Novartis Healthcare Private Limited 
Address  7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East)

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Scientific Query  
Name  Murugananthan K 
Designation  SSO Country Head 
Affiliation  Novartis Healthcare Private Limited 
Address  7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East)

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Details of Contact Person
Public Query  
Name  Murugananthan K 
Designation  Country Monitoring Head 
Affiliation  Novartis Healthcare Private Limited 
Address  7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East)

Mumbai
MAHARASHTRA
400051
India 
Phone  912250243544  
Fax    
Email  murugananthan.k@novartis.com  
 
Source of Monetary or Material Support  
Novartis Pharma AG, Novartis Campus 4056 – Basel, Switzerland 
 
Primary Sponsor  
Name  Novartis Healthcare Pvt Ltd 
Address  Part of 601 and 701, 6 & 7 floor, Inspire BKC, G Block, BKC Main Road, Bandra Kurla Complex, Bandra (East), Mumbai – 400051,India 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Bulgaria
Canada
Czech Republic
France
Germany
Hungary
India
Ireland
Italy
Jordan
Lebanon
Malaysia
Netherlands
Norway
Oman
Republic of Korea
Romania
Singapore
Slovakia
South Africa
Sweden
Switzerland
Turkey
United Arab Emirates
United Kingdom  
Sites of Study  
No of Sites = 5  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Prof Dr Uttam Kumar Nath  AIIMS, Rishikesh,  Department of Medical Oncology Haematology, All India Institute of Medical Sciences (AIIMS), Rishikesh, Yeerbhadra Road, Rishikesh, Uttarakhand, 249203, India."
Uttarkashi
UTTARANCHAL 		 9433982756

nath.uttam@gmail.com 
Dr Maoranjan Mahapatra  AIIMS-Delhi  Department of Hematology 2nd Floor, New Private ward, New Delhi, 110029
North
DELHI 		 8148400246

mrmahapatra@hotmail.com 
Dr Parathan Karunakaran  Cancer Institute W.I.A  Department of Medical oncology, No.38, Sardar Patel Road, Adyar, Chennai-600036, Tamilnadu, India.
Chennai
TAMIL NADU 		 8148400246

drparathan@gmail.com 
Dr Sandip Abhaykumar Shah  Hemato Oncology Clinic Ahmedabad Pvt. Ltd  Vedanta Institute of Medical Science, First floor, Nr. Samved Hospital Stadium Commerce Road, Navrangpura, Ahmedabad-380009,
Ahmadabad
GUJARAT 		 9824041170

sandip60@yahoo.com 
Dr Sujeet Kumar  Homi Bhabha Cancer Hospital  Department of Medical Oncology, Ghanti Mill Road, Lahartara, Old Loco Colony , Shivpurwa, Varanasi , Uttar Pradesh-221010
Varanasi
UTTAR PRADESH 		 7408622706

kumar.sujeet781@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 5  
Name of Committee  Approval Status 
AIIMS Rishikesh Institutional Ethics Committee-Prof. Dr. Uttam Kumar Nath  Approved 
Ethics Committee of Marengo CIMS Hospital-Dr.Sandip Abhaykumar Shah  Approved 
Institutional Ethics Committee AIIMS-Dr.Maoranjan Mahapatra  Approved 
Institutional Ethics Committee Cancer Institute WIA-Dr. Parathan Karunakaran  Approved 
Institutional Ethics Committee MPMMMCC & Homi Bhabha Hospital-Dr.Sujeet Kumar  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C921||Chronic myeloid leukemia, BCR/ABL-positive,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  asciminib  Asciminib 80 mg QD administered under fasting conditions  
Comparator Agent  Nilotinib   Nilotinib 300 mg BID administered under fasting conditions 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Diagnosis of CML-CP (European Leukemia Network [ELN] 2020 criteria) with cytogenetic confirmation of the Philadelphia (Ph) chromosome. A cryptic Ph chromosome should be confirmed by metaphase Fluorescence In Situ Hybridization (FISH)
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,
Platelet (PLT) count ≥ 100 x 109/L (≥ 100,000/mm3),
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. However, if a local qualitative assay, validated according to local regulation, from an accredited local laboratory has confirmed evidence of typical BCR::ABL1 transcript [e14a2 and/or e13a2], these results can be used for eligibility if the central Real Time Quantitative Polymerase Chain Reaction (RQ-PCR) results arrived are not available at the time of randomization.
 
 
ExclusionCriteria 
Details  1Previous 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.
2Known cytopathologically confirmed central nervous system (CNS) infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
3Impaired 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 atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block).
QT interval corrected by Fridericia’s formula (QTcF) ≥ 450 ms (male patients), ≥460 ms (female patients) 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 crediblemeds.org that cannot be discontinued or replaced 7 days prior to starting study treatment 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).
5History of significant congenital or acquired bleeding disorder unrelated to cancer.
6Major surgery within 4 weeks prior to study entry or patients who have not recovered from prior surgery.
7History 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.
8History 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 (deoxyribonucleic acid) 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.
1History of Human Immunodeficiency Virus (HIV) unless well-controlled on a stable dose of anti-retroviral therapy at the time of screening.
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study treatment (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).
Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer.
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for a period of time after stopping study medication. For asciminib, this period of time is 3 days after last dose; if local regulations or locally approved prescribing information differ from the protocol required duration of contraception, the longer duration must be followed and the same requirements will be described in the Informed Consent Form (ICF). Participants taking nilotinib should be willing to follow contraception requirements in the locally-applicable prescribing information for nilotinib.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
The primary objective of the study is to assess the tolerability of asciminib versus nilotinib, in participants with newly diagnosed CML-CP, with respect to the time to discontinuation of study treatment due to adverse event (TTDAE).  time from the date of first dose of study treatment to the date of discontinuation of study treatment due to adverse event (AE) 
 
Secondary Outcome  
Outcome  TimePoints 
MMR   all scheduled data collection time points. 
 
Target Sample Size   Total Sample Size="541"
Sample Size from India="25" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   04/08/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  20/10/2022 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="5"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

The primary purpose of this Phase IIIb study CABL001J12302 is to focus on the patient relevant outcomes and to assess the tolerability of asciminib, as it translates in study treatment discontinuations due to adverse events (AEs), in comparison with that of the second generation (2G) Tyrosine Kinase Inhibitor (TKI) nilotinib, in adult patients with newly diagnosed Ph+ CML-CP. The study also aims to assess treatment impact on quality of life. Generating such data is patient relevant as well as deemed important for Health Technology Assessment (HTA) bodies’ decision making. . It is planned to randomize approximately 541 patients in the study in a 1:1 randomization to asciminib or nilotinib. Randomization will be stratified based on European Treatment Outcome Study (EUTOS) long-term survival (ELTS) score (low versus intermediate versus high) to help achieve a balance between the treatment arms. Asciminib has been shown to be highly selective against BCR::ABL1-positive cell lines when compared with imatinib, nilotinib, dasatinib, and bosutinib, which vary considerably in their degree of specificity. The study also aims to assess treatment impact on quality of life. Generating such data is patient relevant as well as deemed important for Health Technology Assessment (HTA) bodies’ decision making.


 
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