A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)

NCT05456191 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CABL001J123022024-510947-71-00
• Study Type: interventional
• Target: 568
• Locations: 24 countries
• Sites: 120

Brief Summary

The primary purpose of this study was to assess the tolerability of oral asciminib (80 mg QD) in comparison with that of the second generation (2G) Tyrosine Kinase Inhibitor (TKI) nilotinib (300 mg BID), in adult patients with newly diagnosed Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).

Conditions

Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

Keywords

Asciminib (ABL001); Abelson proto-oncogene (ABL); newly diagnosed 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; Chronic Myeloproliferative Disorders; Philadelphia chromosome; Nilotinib; Leukemia; Phase 3; Tyrosine Kinase Inhibitor (TKI); Treatment Free Remission (TFR); Treatment Re-initiation (TRI)

Outcome Measures

Primary Outcomes (1)

• Time to discontinuation of study treatment due to adverse event (TTDAE).

  TTDAE is defined as the time from the date of first dose of study treatment to the date of discontinuation of study treatment due to adverse event (AE).

  From date of first dose to date of treatment discontinuation due to AE, assessed up to 5 years

Secondary Outcomes (23)

• Percentage of participants with Major Molecular response (MMR) at scheduled data collection time points

  approximately 7.5 years

• Percentage of participants with Major Molecular response (MMR) by scheduled data collection time points

  approximately 7.5 years

• Percentage of participants with MR4.0 at scheduled data collection time points

  approximately 7.5 years

• Percentage of participants with MR4.0 by scheduled data collection time points

  approximately 7.5 years

• Percentage of participants with MR4.5 at scheduled data collection time points

  approximately 7.5 years

Study Arms (2)

Asciminib

EXPERIMENTAL

Participants received asciminib 80 mg once a day (QD).

Drug: Asciminib

Nilotinib

ACTIVE COMPARATOR

Participants will receive nilotinib 300 mg BID

Drug: Nilotinib

Interventions

Asciminib DRUG

Asciminib 80 mg QD administered under fasting conditions.

Also known as: ABL001

Asciminib

Nilotinib DRUG

Nilotinib 300 mg twice a day (BID) was administered under fasting conditions.

Nilotinib

Eligibility Criteria

• Age: 18 Years - 100 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 ≥ 18 years of age.
• Patients with CML-CP within 3 months of diagnosis.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate end organ function as defined by:
• Total bilirubin (TBL) \< 3 x Upper Limit of Normal (ULN); patients with Gilbert's syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN,
• Creatinine Clearance (CrCl) ≥ 30 milliliters per minute (mL/min) as calculated using Cockcroft-Gault formula, Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis.

You may not qualify if:

• Previous 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.
• Known cytopathologically confirmed central nervous system (CNS) infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
• Impaired 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 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).
• History of significant congenital or acquired bleeding disorder unrelated to cancer.
• Major surgery within 4 weeks prior to study entry or patients who have not recovered from prior surgery.
• History 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.
• History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (120)

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Illinois Cancer Care

Peoria, Illinois, 61615, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Messino Cancer Centers

Asheville, North Carolina, 28806, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Williamette Cancer Center

Eugene, Oregon, 97401, United States

Location

Texas Oncology P A

Bedford, Texas, 76022, United States

Location

Texas Oncology PA Bedford

Bedford, Texas, 76022, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1221ADH, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1114AAN, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1425AUM, Argentina

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Novartis Investigative Site

Caba, C1039AAC, Argentina

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Novartis Investigative Site

CABA, C1181ACH, Argentina

Location

Novartis Investigative Site

Pleven, 5800, Bulgaria

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Novartis Investigative Site

Plovdiv, 4002, Bulgaria

Location

Novartis Investigative Site

Sofia, 1431, Bulgaria

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Novartis Investigative Site

Sofia, 1797, Bulgaria

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Novartis Investigative Site

Varna, 9010, Bulgaria

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Novartis Investigative Site

London, Ontario, N6A 5W9, Canada

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Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Brno, 625 00, Czechia

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Novartis Investigative Site

Plzen Bory, 301 00, Czechia

Location

Novartis Investigative Site

Prague, 100 34, Czechia

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Novartis Investigative Site

Prague, 128 00, Czechia

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Novartis Investigative Site

Bordeaux, 33076, France

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Novartis Investigative Site

Caen, 14033, France

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Novartis Investigative Site

Clermont-Ferrand, 63003, France

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Lyon, 69373, France

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Novartis Investigative Site

Marseille, 13273, France

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Novartis Investigative Site

Nantes, 44093, France

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Novartis Investigative Site

Nice, 06202, France

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Novartis Investigative Site

Paris, 75475, France

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Novartis Investigative Site

Poitiers, 86021, France

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Novartis Investigative Site

Strasbourg, 67000, France

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Novartis Investigative Site

Toulouse, 31059, France

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Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

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Novartis Investigative Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Novartis Investigative Site

Mannheim, Baden-Wurttemberg, 68305, Germany

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Novartis Investigative Site

Munich, Bavaria, 81241, Germany

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Novartis Investigative Site

Würzburg, Bavaria, 97080, Germany

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Novartis Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

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Novartis Investigative Site

Marburg, Hesse, 35043, Germany

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Novartis Investigative Site

Paderborn, North Rhine-Westphalia, 33098, Germany

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Novartis Investigative Site

Velbert, North Rhine-Westphalia, 42551, Germany

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Novartis Investigative Site

Dresden, Saxony, 01307, Germany

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Leipzig, Saxony, 04103, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Jena, Thuringia, 07740, Germany

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Aachen, 52074, Germany

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Novartis Investigative Site

Augsburg, 86179, Germany

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Novartis Investigative Site

Bad Saarow, 15526, Germany

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Novartis Investigative Site

Bayreuth, 95445, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Bonn, 53105, Germany

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Novartis Investigative Site

Bremen, 28205, Germany

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Novartis Investigative Site

Chemnitz, 09113, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Hamburg, 20246, Germany

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Hanover, 30161, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Lübeck, 23538, Germany

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Novartis Investigative Site

Magdeburg, 39104, Germany

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Novartis Investigative Site

München, 80377, Germany

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Novartis Investigative Site

Regensburg, 93049, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Ulm, 89081, Germany

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Novartis Investigative Site

Athens, 106 76, Greece

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Novartis Investigative Site

Athens, 115 27, Greece

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Novartis Investigative Site

Ioannina, 455 00, Greece

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Novartis Investigative Site

Pátrai, 265 04, Greece

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Novartis Investigative Site

Thessaloniki, 570 10, Greece

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Novartis Investigative Site

Budapest, H-1083, Hungary

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Novartis Investigative Site

Budapest, H-1097, Hungary

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Novartis Investigative Site

Eger, 3300, Hungary

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Novartis Investigative Site

Ahmedabad, Gujarat, 380009, India

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Novartis Investigative Site

New Delhi, National Capital Territory of Delhi, 110029, India

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Novartis Investigative Site

Chennai, Tamil Nadu, 600036, India

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Varanasi, Uttar Pradesh, 221010, India

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Novartis Investigative Site

Rishikesh, Uttarakhand, 249203, India

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Novartis Investigative Site

Meldola, FC, 47014, Italy

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Novartis Investigative Site

Milan, MI, 20162, Italy

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Novartis Investigative Site

Pisa, PI, 56126, Italy

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Novartis Investigative Site

Roma, RM, 00144, Italy

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Novartis Investigative Site

Torino, TO, 10126, Italy

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Novartis Investigative Site

Amman, 11941, Jordan

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Novartis Investigative Site

Alor Star, Kedah, 05460, Malaysia

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Novartis Investigative Site

Kuching, Sarawak, 93586, Malaysia

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Novartis Investigative Site

Petaling Jaya, Selangor, 46150, Malaysia

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Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

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Novartis Investigative Site

Dordrecht, South Holland, 3318 AT, Netherlands

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Novartis Investigative Site

Khoudh, 123, Oman

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Novartis Investigative Site

Cluj-Napoca, Cluj, 400015, Romania

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Novartis Investigative Site

Craiova, Dolj, 200136, Romania

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Novartis Investigative Site

Târgu Mureş, Mureș County, 540136, Romania

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Novartis Investigative Site

Bucharest, 021494, Romania

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Novartis Investigative Site

Bucharest, 022328, Romania

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Novartis Investigative Site

Bucharest, 030 171, Romania

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Novartis Investigative Site

Sibiu, 550245, Romania

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Novartis Investigative Site

Timișoara, 300079, Romania

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Novartis Investigative Site

Singapore, 119074, Singapore

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Novartis Investigative Site

Singapore, 169608, Singapore

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Novartis Investigative Site

Singapore, S308433, Singapore

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Novartis Investigative Site

Bratislava, 851 07, Slovakia

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Novartis Investigative Site

Johannesburg, Gauteng, 2013, South Africa

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Novartis Investigative Site

Pretoria, Gauteng, 0181, South Africa

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Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

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Novartis Investigative Site

Uijeongbu-si, Gyeonggi-do, 11759, South Korea

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Novartis Investigative Site

Geneva, 1211, Switzerland

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Novartis Investigative Site

Istanbul, Fatih, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, Sihhiye-Altindag, 06230, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35100, Turkey (Türkiye)

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Novartis Investigative Site

Abu Dhabi, 00000, United Arab Emirates

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Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

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Novartis Investigative Site

Gloucester, GL1 3NN, United Kingdom

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Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Novartis Investigative Site

London, W12 0HS, United Kingdom

Location

Novartis Investigative Site

Newport, NP20 2UB, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Philadelphia Chromosome; Leukemia

Interventions

asciminib; nilotinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 13, 2022
• Study Start: November 21, 2022
• Primary Completion: May 15, 2025
• Study Completion (Estimated): July 7, 2031
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

AE (1); CZ (4); RO (8); CA (2); SL (1); GB (5); HU (3); JO (1); NL (1); AR (5); OM (1); FR (13); ZA (2); MY (4); KR (2); US (9); DE (31); BU (5); GR (5); IT (5); IN (5); SG (3); CH (1); TU (3)