Asciminib Treatment Optimization in ≥ 3rd Line CML-CP.

A Phase 3b, Multi-center, Open-label, Treatment Optimization Study of Oral Asciminib in Patients With Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Previously Treated With 2 or More Tyrosine Kinase Inhibitors.

ClinicalTrials.gov Identifier: NCT04948333

Novartis Reference Number: CABL001A2302

Last Update: Nov 14, 2022

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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 purpose of the study is to optimize the treatment of asciminib in patients with chronic myelogenous leukemia in chronic phase (CML-CP) previously treated with 2 or more Tyrosine Kinase Inhibitors (TKIs). Patients for this study will be identified based on warning criteria and resistance definition following European Leukemia Network (ELN) 2020 recommendations.

In addition, the study will investigate the use of two different posologies. For this, patients will receive asciminib 40 mg (twice-daily) BID or of 80 mg (once daily) once daily (QD).

Condition 
Chronic Myelogenous Leukemia
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Oct 13, 2021
Completion date 
Jun 11, 2026
Gender 
All
Age(s)
18 Years - 99 Years (Adult, Older Adult)

Interventions

Drug
ABL001 40mg BID
One tablet of 40 mg will be taken orally twice a day (BID)
Drug
ABL001 80mg QD
Two tablets of 40 mg will be taken orally once a day (QD)
Drug
ABL001 200mg QD
Five tablets of 40 mg will be taken orally once a day (QD)

Eligibility Criteria

Inclusion criteria:

Male or female patients with a diagnosis of CML-CP ≥ 18 years of age

Patients must meet all 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 109/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 Prior treatment with a minimum of 2 prior TKIs (i.e. imatinib, nilotinib, dasatinib, bosutinib, radotinib or ponatinib) Warning or failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening

Warning is defined as:

Three months after the initiation of treatment: BCR-ABL1 > 10% IS
Six months after the initiation of treatment: BCR-ABL1 >1-10% IS
Twelve months after the initiation of treatment BCR-ABL1>0,1-1% IS
At any time after the initiation of therapy BCR-ABL1 >0.1-1% IS, loss of MMR (>0.1% with 5-fold increase of BCR-ABL1 transcripts).

In addition, patients with failure of treatment according to the ELN 2020 recommendations will be eligible:

Three months after the initiation of treatment: BCR-ABL1 > 10% IS if confirmed within 1-3 months
Six months after the initiation of treatment: BCR-ABL1 >10% IS
Twelve months after the initiation of treatment BCR-ABL1 >1% IS
At any time after the initiation of therapy BCR-ABL1 >1% IS, emergence of resistance mutations, high-risk ACA

Intolerance is defined as:

Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)
Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer

Exclusion criteria:

Known presence of the BCR-ABL1 T315I mutation at any time prior to study entry. Known history of AP/BC Previous treatment with a hematopoietic stem-cell transplantation Patient planning to undergo allogeneic hematopoietic stem cell transplantation

Cardiac or cardiac repolarization abnormality, including any 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, permanent pace maker)
QTcF at screening ≥450 msec (male patients), ≥460 msec (female patients)

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, pulmonary hypertension) History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis History of active ongoing acute or chronic liver disease Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 days after last dose of asciminib.

Other Inclusion/Exclusion criteria may apply.

Study Locations

Argentina
Novartis Investigative Site
Recruiting
Caba, C1221ADC
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Buenos Aires, C1114AAN
-
Argentina
Austria
Novartis Investigative Site
Recruiting
Graz, 8036
-
Austria
Novartis Investigative Site
Recruiting
Linz, 4010
-
Austria
Novartis Investigative Site
Recruiting
Wien, 1140
-
Austria
Canada
Novartis Investigative Site
Recruiting
Vancouver, V5Z 1M9
British Columbia
Canada
Novartis Investigative Site
Recruiting
Quebec, G1J 1Z4
-
Canada
France
Novartis Investigative Site
Recruiting
Bordeaux, 33076
-
France
Novartis Investigative Site
Recruiting
Lyon Cedex, 69373
-
France
Novartis Investigative Site
Recruiting
Montpellier cedex 5, 34295
-
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
Berlin, 13353
-
Germany
Novartis Investigative Site
Recruiting
Frankfurt, 60590
-
Germany
Novartis Investigative Site
Recruiting
Jena, 07740
-
Germany
Novartis Investigative Site
Recruiting
Kiel, 24116
-
Germany
Novartis Investigative Site
Recruiting
Muenchen, 80377
-
Germany
Greece
Novartis Investigative Site
Recruiting
Thessaloniki, 570 10
GR
Greece
Novartis Investigative Site
Recruiting
Athens, 115 27
-
Greece
Italy
Novartis Investigative Site
Recruiting
Monza, 20900
MB
Italy
Novartis Investigative Site
Recruiting
Roma, 00144
RM
Italy
Novartis Investigative Site
Recruiting
Roma, 00161
RM
Italy
Novartis Investigative Site
Recruiting
Verona, 37126
VR
Italy
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
Novartis Investigative Site
Recruiting
Taegu, 41944
-
Korea, Republic of
Malaysia
Novartis Investigative Site
Recruiting
Kota Kinabalu, 88586
Sabah
Malaysia
Novartis Investigative Site
Recruiting
Johor Bahru, 80100
-
Malaysia
Novartis Investigative Site
Recruiting
Penang, 10990
-
Malaysia
Novartis Investigative Site
Recruiting
Selangor, 68000
-
Malaysia
Oman
Novartis Investigative Site
Recruiting
Muscat, 123
-
Oman
Poland
Novartis Investigative Site
Recruiting
Katowice, 40-519
-
Poland
Novartis Investigative Site
Recruiting
Krakow, 31-503
-
Poland
Novartis Investigative Site
Recruiting
Warszawa, 02 776
-
Poland
Singapore
Novartis Investigative Site
Recruiting
Singapore, 119074
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, 169608
-
Singapore
Novartis Investigative Site
Recruiting
Singapore, S308433
-
Singapore
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
Novartis Investigative Site
Recruiting
Santiago de Compostela, 15706
Galicia
Spain
Novartis Investigative Site
Recruiting
Bilbao, 48013
Pais Vasco
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain
Novartis Investigative Site
Recruiting
Santa Cruz de Tenerife, 38009
-
Spain
United Kingdom
Novartis Investigative Site
Recruiting
Cambridge, CB2 2QQ
-
United Kingdom
Novartis Investigative Site
Recruiting
Leeds, LS9 7TF
-
United Kingdom
Novartis Investigative Site
Recruiting
London, SE1 9RT
-
United Kingdom
Novartis Investigative Site
Recruiting
London, W12 0HS
-
United Kingdom
Vietnam
Novartis Investigative Site
Recruiting
Hanoi, 100000
-
Vietnam
Novartis Investigative Site
Recruiting
Ho Chi Minh City, DISTRICT 1
-
Vietnam

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals

Have a question?

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