Clinical trial NCT04795427: Study of Efficacy and Safety of CML-CP Patients Treated With Asciminib Versus Best Available Therapy, Previously Treated With 2 or More Tyrosine Kinase Inhibitors
Official title: A Randomized, Open-label, Multi-center, Phase II Study of Asciminib Versus Best Available Therapy in Chinese Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated With 2 or More Tyrosine Kinase Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Chronic Myelogenous
Keywords: Chronic Myelogenous Leukemia in chronic phase
Chronic Myelogenous Leukemia
CML-CP
Chronic
Chronic Phase
ABL001
asciminib
prior treatment with 2 or more tyrosine kinase inhibitors (TKIs)
major molecular response
MMR
Chinese patients
phase ll
open label
best available therapy
BAT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics of asciminib versus best available therapy in Chinese patients with Chronic Myelogenous Leukemia in chronic phase, previously treated with 2 or more tyrosine kinase inhibitors to support related indication registration in China.

The primary objective of the study is to evaluate the Major Molecular Response (MMR) rate of asciminib treatment at 24 weeks.

Detailed description: The purpose of this Chinese bridging study is to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of asciminib versus best available therapy (BAT) in Chinese patients with Chronic Myelogenous Leukemia in chronic phase (CML-CP), previously treated with 2 or more tyrosine kinase inhibitors (TKIs) to support related indication registration in China.

This study will enroll the participants 1) who failed their most recent TKI therapy by meeting the definition of treatment failure as per the 2013 European Leukemia Net (ELN) guidelines, or 2) who were intolerant to the most recent TKI therapy and must have BCR-ABL1 ratio \> 0.1% IS at screening.

Eligible participants will be randomized into asciminib arm or the BAT arm on a 2:1 ratio, to receive asciminib treatment (continuous 40 mg BID) or BAT from Day 1 until the end of study treatment period defined as 96 weeks after the last participant receives the first dose.

Eligibility criteria: Inclusion Criteria:

Diagnosed as CML-CP:

1. Participants must meet all of the following laboratory values at the screening visit:

   \< 15% blasts in peripheral blood and bone marrow \< 30% blasts plus promyelocytes in peripheral blood and bone marrow \< 20% basophils in the peripheral blood
   * 50 x 10\^9/ L (≥ 50,000/mm3) platelets Transient prior therapy related thrombocytopenia (\< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
2. Prior treatment with a minimum of 2 prior ATP-competitive TKIs.
3. Failure (adapted from the 2013 European Leukemia Net (ELN) Guidelines) or intolerance to the most recent TKI therapy at the time of screening.
4. Evidence of typical BCR-ABL1 transcript \[e14a2 and/or e13a2\] at the time of screening which are amenable to standardized RQ-PCR quantification

Exclusion Criteria:

1. Known presence of the T315I mutation at any time prior to study entry
2. Known second chronic phase of CML after previous progression to AP/BC
3. Previous treatment with a hematopoietic stem cell transplantation
4. Participants planning to undergo allogeneic hematopoietic stem cell transplantation
5. Cardiac or cardiac repolarization abnormality, including any of the following:

   History within 6 months prior to starting study treatment of myocardial infarction, angina pectoris, coronary artery bypass graft Clinically significant cardiac arrhythmias , complete left bundle branch block, high-grade AV block QTcF at screening ≥450 msec (male participants), ≥460 msec (female participants)

   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 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" that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.

   Inability to determine the QTcF interval
6. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Major molecular response rate of asciminib
timeFrame: week 24
Secondary outcomes:
measure: Cytogenetic response (CyR) rate
timeFrame: 24, 48, 96 weeks
measure: Major molecular response rate of best available treatment arm
timeFrame: week 24
measure: Major molecular response rate of both asciminib arm and BAT armn time points
timeFrame: Up to all participants received at least 96 weeks of randomized study treatment, except week 24
measure: major molecular response rate by all scheduled data collection time points
timeFrame: Up to all participants received at least 96 weeks of randomized study treatment
measure: Time to major molecular response rate
timeFrame: Up to all participants received at least 96 weeks of randomized study treatment
measure: Duration of major molecular response
timeFrame: Up to all participants received at least 96 weeks of randomized study treatment
measure: Overall survival
timeFrame: Up to all participants received at least 96 weeks of randomized study treatment, plus 30 days for safety follow up
measure: Progression free survival
timeFrame: Up to all participants received at least 96 weeks of randomized study treatment, plus 30 days for safety follow up
measure: Pharmacokinetics (PK) parameter of asciminib: Cmax
timeFrame: Week 2 Day 1 (W2D1)
measure: PK parameter of asciminib: Tmax
timeFrame: Week 2 Day 1 (W2D1)
measure: PK parameter of asciminib: Ctrough
timeFrame: Week 2 Day 1 (W2D1)
measure: PK parameter of asciminib: AUCtau
timeFrame: Week 2 Day 1 (W2D1)
measure: PK parameter of asciminib: AUClast
timeFrame: Week 2 Day 1 (W2D1)
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Novartis Investigative Site
state: Chongqing
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shenzhen
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Zhengzhou
country: China
facility: Novartis Investigative Site
state: Henan
city: Zhengzhou
country: China
facility: Novartis Investigative Site
state: Henan
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nantong
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Wenzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shenyang
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: