Asciminib Treatment Optimization in ≥ 3rd Line CML-CP

NCT04948333 | Completed Phase 3 Results

• 2 other identifiers: CABL001A23022024-511381-36-00
• Study Type: interventional
• Target: 199
• Locations: 16 countries
• Sites: 48

Brief Summary

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).

Conditions

Chronic Myelogenous Leukemia

Keywords

ABL001; Phase 3; tyrosine kinase inhibitor; Chronic myelogenous leukemia (CML); chronic myeloid leukemia (CML); chronic myelocytic leukemia (CML); chronic granulocytic leukemia (CGL); cancer of the white blood cells; clonal bone marrow stem cell disorder; proliferation of mature granulocytes; Treatment optimization; Asciminib; European Leukemia Network (ELN) Recommendations 2020; Major Molecular Response (MMR) rate at 48 weeks

Outcome Measures

Primary Outcomes (1)

• Major Molecular Response (MMR) Rate at Week 48 for All Patients With no Evidence of MMR at Baseline

  Major Molecular Response (MMR) is defined as a significant reduction in the level of BCR::ABL1 transcripts, which are the genetic markers of chronic myeloid leukemia (CML). Specifically, MMR is achieved when there is a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to a standardized baseline, which corresponds to a BCR::ABL1/ABL1 ratio of ≤ 0.1% on the international scale (IS). The Major Molecular Response (MMR) rate at Week 48 for all patients with no evidence of MMR at baseline refers to the percentage of patients who achieve MMR after 48 weeks of treatment, despite not having MMR at the start.

  Week 48

Secondary Outcomes (20)

• MMR Rate at Week 12, 24, 36, 72, 96 and 144 for Patients With no MMR at Baseline

  Week 12, 24, 36, 72, 96 and 144

• Major Molecular Response (MMR) Rate at Week 48 for Patients With MMR at Baseline

  Week 48.

• Time to MMR for Subjects Without MMR at Baseline

  From the date of enrollment to the date of first documented MMR, assessed up to 144 weeks

• Rate of BCR::ABL1 ≤ 10% for Subjects Without MMR at Baseline

  Week 12, 24, 36 and 48

• Rate of BCR::ABL1 ≤ 1% for Subjects Without MMR at Baseline

  Week 12, 24, 36 and 48.

Study Arms (1)

ABL001

EXPERIMENTAL

Participants will be treated with 80 mg of ABL001 (40 mg BID or 80mg QD). In patients not achieving MMR at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation.

Drug: ABL001 40mg BID; Drug: ABL001 80mg QD; Drug: ABL001 200mg QD

Interventions

ABL001 40mg BID DRUG

One tablet of 40 mg will be taken orally twice a day (BID)

Also known as: asciminib

ABL001

ABL001 80mg QD DRUG

Two tablets of 40 mg will be taken orally once a day (QD)

Also known as: asciminib

ABL001

ABL001 200mg QD DRUG

Five tablets of 40 mg will be taken orally once a day (QD)

Also known as: asciminib

ABL001

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent must be obtained prior to participation in the study
• Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
• Treatment with a minimum of 2 or more 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
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
• Adequate end organ function (as per central laboratory tests)

You may not qualify if:

• Known presence of the BCR::ABL1 T315I mutation at any time prior to study entry
• Known second chronic phase of CML after previous progression to AP/BC
• Previous treatment with a hematopoietic stem-cell transplantation
• Patient planning to undergo allogeneic hematopoietic stem cell transplantation
• Uncontrolled cardiac repolarization abnormality
• 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
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• Testing for Hepatitis B surface antigen (HbsAg) and Hepatitis B core antibody (HBcAb / anti HBc) will be performed at screening. Patients with active Hepatitis B Virus (HBV) infection (hepatitis B surface antigen \[HbsAg\] positive) will be excluded

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (48)

Novartis Investigative Site

CABA, Buenos Aires, C1221ADC, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1114AAN, Argentina

Location

Novartis Investigative Site

Graz, 8036, Austria

Location

Novartis Investigative Site

Linz, 4010, Austria

Location

Novartis Investigative Site

Vienna, 1140, Austria

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20211-030, Brazil

Location

Novartis Investigative Site

São Paulo, 01227-200, Brazil

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Bordeaux, 33076, France

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

Location

Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

Location

Novartis Investigative Site

Jena, Thuringia, 07740, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Kiel, 24116, Germany

Location

Novartis Investigative Site

München, 80377, Germany

Location

Novartis Investigative Site

Athens, 115 27, Greece

Location

Novartis Investigative Site

Thessaloniki, 570 10, Greece

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Verona, VR, 37134, Italy

Location

Novartis Investigative Site

George Town, Pulau Pinang, 10450, Malaysia

Location

Novartis Investigative Site

Kota Kinabalu, Sabah, 88586, Malaysia

Location

Novartis Investigative Site

Johor Bahru, 80100, Malaysia

Location

Novartis Investigative Site

Kuala Selangor, 68000, Malaysia

Location

Novartis Investigative Site

Khoudh, 123, Oman

Location

Novartis Investigative Site

Katowice, 40-519, Poland

Location

Novartis Investigative Site

Warsaw, 00-791, Poland

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Taegu, 41944, South Korea

Location

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

Location

Novartis Investigative Site

Bilbao, Bizkaia, 48013, Spain

Location

Novartis Investigative Site

Santa Cruz, Santa Cruz De Tenerife, 38009, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

Cambridge, CB2 0QQ, United Kingdom

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Novartis Investigative Site

London, W12 0HS, United Kingdom

Location

Novartis Investigative Site

Hanoi, 100000, Vietnam

Location

Novartis Investigative Site

Ho Chi Minh City, 70000, Vietnam

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib; BID protein, human

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 1, 2021
• Study Start: October 13, 2021
• Primary Completion: March 12, 2024
• Study Completion: February 25, 2026
• Last Updated: March 18, 2026
• Results First Posted: March 27, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

GR (2); AU (3); IT (3); ES (5); VN (2); CA (2); MY (4); SG (2); OM (1); FR (5); KR (3); DE (6); GB (4); BR (2); AR (2); PL (2)