A study to investigate the effect of asciminib versus nilotinib in adult patients with Leukemia

Phase 3

Recruiting

• Conditions: Chronic myeloid leukemia, BCR/ABL-positive,

• Registration Number: CTRI/2023/07/054677
• Lead Sponsor: Novartis Healthcare Pvt Ltd

Brief Summary

The primary purpose of this Phase IIIb study CABL001J12302 is tofocus on the patient relevant outcomes and to assess the tolerability ofasciminib, as it translates in study treatment discontinuations due to adverseevents (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 alsoaims to assess treatment impact on quality of life. Generating such data ispatient relevant as well as deemed important for Health Technology Assessment(HTA) bodies’ decision making. . It is planned to randomize approximately 541 patients in thestudy in a 1:1 randomization to asciminib or nilotinib. Randomization will bestratified based on European Treatment Outcome Study(EUTOS)long-term survival (ELTS) score (low versus intermediate versus high) tohelp achieve a balance between the treatment arms. Asciminibhas been shown to be highly selective against *BCR::ABL1*-positive celllines when compared with imatinib, nilotinib, dasatinib, and bosutinib, whichvary considerably in their degree of specificity. Thestudy also aims to assess treatment impact on quality of life. Generating suchdata is patient relevant as well as deemed important for Health TechnologyAssessment (HTA) bodies’ decision making.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-08
• Last Update Posted: 2024-12-01

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 541

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
MMR	all scheduled data collection time points.

Trial Locations

Locations (5)

AIIMS, Rishikesh,; 🇮🇳 Uttarkashi, UTTARANCHAL, India

AIIMS-Delhi; 🇮🇳 North, DELHI, India

Cancer Institute W.I.A; 🇮🇳 Chennai, TAMIL NADU, India

Hemato Oncology Clinic Ahmedabad Pvt. Ltd; 🇮🇳 Ahmadabad, GUJARAT, India

Homi Bhabha Cancer Hospital; 🇮🇳 Varanasi, UTTAR PRADESH, India

AIIMS, Rishikesh,

🇮🇳Uttarkashi, UTTARANCHAL, India

Prof Dr Uttam Kumar Nath

Principal investigator

9433982756

nath.uttam@gmail.com