AzTrials
AzTrials

Philadelphia Chromosome-Positive Chronic Myeloid LeukemiaPhase 3ASC4STARTNCT05456191

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)

A Phase 3 study testing Asciminib and Nilotinib in people with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 119 sites in 24 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Asciminib and Nilotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
568 participants
Where
119 sitesin 24 countries
Study dates
21 Nov 2022to 7 Jul 2031
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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.
  • Patients must have the following laboratory values within normal limits or corrected to within normal limits with supplements prior to randomization:
  • Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with CrCl* ≥ 90 mL/min)**,
  • Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with CrCl* ≥ 90 mL/min),
  • Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl* ≥ 90 mL/min),
  • For patients with mild to moderate renal impairment (CrCl* ≥ 30 mL/min and <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be within normal limits or corrected to within normal limits with supplements prior to randomization.
  • CrCl as calculated using Cockcroft-Gault formula.
  • pseudohyperkaliemia in case of thrombocytosis is not an exclusion criterion.
  • Inclusion Criteria for optional Treatment Free Remission (TFR) Phase:
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
  • A minimum of 3 years (156 weeks) of treatment on study, up-to maximum of 5 years (260 weeks) of treatment.
  • Sustained MR4.5 (BCR:ABL1 ≤0.0032% IS) for at least 1 year (≥52 weeks) immediately prior to entry into the TFR Phase, defined as 5 consecutive (every 12 weeks) central laboratory RQ-PCR assessments at MR4.5 or below for the course of at least a year. Entry into TFR Phase should be at an unscheduled visit or next scheduled visit no later than 12 Weeks from the last RQ-PCR assessment date at MR4.5 or lower.
  • Separate signed informed consent must be obtained prior to participation in the TFR Phase.

Who cannot join

  • 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.
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  • 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.
  • 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 10.4
  • History 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). Participants taking nilotinib should be willing to follow contraception requirements in the locally-applicable prescribing information for nilotinib.
  • Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy or bilateral salpingectomy, at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  • Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks before taking study treatment).
  • Male partner's sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant
  • Use of combined, estrogen and progesterone hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal. Progesterone only hormonal contraception associated with inhibition of ovulation: oral, injected or implanted, or placement of an intrauterine device (IUD) or intrauterine system (IUS).
  • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
  • Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate history of vasomotor symptoms). Women are considered not of child bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks prior to enrollment on the study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered to be not of child bearing potential.
  • Sexually active males taking study treatment do not require contraception. - Known hypersensitivity to the study treatment. Note: The Investigator has the discretion to include/exclude a patient in the study, who will be found to have symptoms representative of coronavirus disease of 2019 (COVID-19) or tested positive for COVID-19 during the screening phase. Such patients should be managed as per the country specific guidelines related to COVID-19. For patients who test positive for COVID-19, re-testing is recommended before initiating study treatment.
  • Exclusion Criteria for optional Treatment Free Remission (TFR) Phase:
  • Participants in the TRI Phase cannot re-enter the TFR Phase for second attempt TFR.
  • In case of a pregnancy or nursing (lactating) during the TFR Phase, the female participant must be discontinued from the study upon loss of MMR (>0.1% BCR::ABL1 IS at a single assessment) and cannot enter the TRI Phase.
  • Relevant exclusion criteria for treatment phase apply including but not limited to:
  • Impaired cardiac function or 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.
  • 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).

Trial locations and contacts

119 sites in 24 countries.

119 sites in 24 countries

Germany31 sites

  • Novartis Investigative Site

    Aachen, 52074

  • Novartis Investigative Site

    Augsburg, 86179

  • Novartis Investigative Site

    Bad Saarow, 15526

  • Novartis Investigative Site

    Bayreuth, 95445

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Bonn, 53105

  • Novartis Investigative Site

    Bremen, 28205

  • Novartis Investigative Site

    Chemnitz, 09113

  • Novartis Investigative Site

    Dresden, Saxony, 01307

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Frankfurt am Main, Hesse, 60590

  • Novartis Investigative Site

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Novartis Investigative Site

    Halle, Saxony-Anhalt, 06120

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Hanover, 30161

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    Jena, Thuringia, 07740

  • Novartis Investigative Site

    Leipzig, Saxony, 04103

  • Novartis Investigative Site

    Lübeck, 23538

  • Novartis Investigative Site

    Magdeburg, 39104

  • Novartis Investigative Site

    Mannheim, Baden-Wurttemberg, 68305

  • Novartis Investigative Site

    Marburg, Hesse, 35043

  • Novartis Investigative Site

    München, 80377

  • Novartis Investigative Site

    Munich, Bavaria, 81241

  • Novartis Investigative Site

    Paderborn, North Rhine-Westphalia, 33098

  • Novartis Investigative Site

    Regensburg, 93049

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Ulm, 89081

  • Novartis Investigative Site

    Velbert, North Rhine-Westphalia, 42551

  • Novartis Investigative Site

    Würzburg, Bavaria, 97080

Other trials in Germany

France13 sites

  • Novartis Investigative Site

    Bordeaux, 33076

  • Novartis Investigative Site

    Caen, 14033

  • Novartis Investigative Site

    Clermont-Ferrand, 63003

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Nice, 06202

  • Novartis Investigative Site

    Paris, 75475

  • Novartis Investigative Site

    Poitiers, 86021

  • Novartis Investigative Site

    Strasbourg, 67000

  • Novartis Investigative Site

    Toulouse, 31059

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

United States9 sites

  • Messino Cancer Centers

    Asheville, North Carolina, 28806

  • Texas Oncology P A

    Bedford, Texas, 76022

  • Texas Oncology PA Bedford

    Bedford, Texas, 76022

  • Oncology Hematology Care Inc

    Cincinnati, Ohio, 45242

  • Rocky Mountain Cancer Centers

    Denver, Colorado, 80218

  • Williamette Cancer Center

    Eugene, Oregon, 97401

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Illinois Cancer Care

    Peoria, Illinois, 61615

  • Regions Hospital

    Saint Paul, Minnesota, 55101

Other trials in United States

Romania8 sites

  • Novartis Investigative Site

    Bucharest, 021494

  • Novartis Investigative Site

    Bucharest, 022328

  • Novartis Investigative Site

    Bucharest, 030 171

  • Novartis Investigative Site

    Cluj-Napoca, Cluj, 400015

  • Novartis Investigative Site

    Craiova, Dolj, 200136

  • Novartis Investigative Site

    Sibiu, 550245

  • Novartis Investigative Site

    Târgu Mureş, Mureș County, 540136

  • Novartis Investigative Site

    Timișoara, 300079

Other trials in Romania

Argentina5 sites

  • Novartis Investigative Site

    Buenos Aires, C1039AAC

  • Novartis Investigative Site

    Buenos Aires, C1114AAN

  • Novartis Investigative Site

    Buenos Aires, C1425AUM

  • Novartis Investigative Site

    CABA, Buenos Aires, C1221ADH

  • Novartis Investigative Site

    CABA, C1181ACH

Other trials in Argentina

Bulgaria5 sites

  • Novartis Investigative Site

    Pleven, 5800

  • Novartis Investigative Site

    Plovdiv, 4002

  • Novartis Investigative Site

    Sofia, 1431

  • Novartis Investigative Site

    Sofia, 1797

  • Novartis Investigative Site

    Varna, 9010

Other trials in Bulgaria

Greece5 sites

  • Novartis Investigative Site

    Athens, 106 76

  • Novartis Investigative Site

    Athens, 115 27

  • Novartis Investigative Site

    Ioannina, 455 00

  • Novartis Investigative Site

    Pátrai, 265 04

  • Novartis Investigative Site

    Thessaloniki, 570 10

Other trials in Greece

India5 sites

  • Novartis Investigative Site

    Ahmedabad, Gujarat, 380009

  • Novartis Investigative Site

    Chennai, Tamil Nadu, 600036

  • Novartis Investigative Site

    New Delhi, National Capital Territory of Delhi, 110029

  • Novartis Investigative Site

    Rishikesh, Uttarakhand, 249203

  • Novartis Investigative Site

    Varanasi, Uttar Pradesh, 221010

Other trials in India

Italy5 sites

  • Novartis Investigative Site

    Meldola, FC, 47014

  • Novartis Investigative Site

    Milan, MI, 20162

  • Novartis Investigative Site

    Pisa, PI, 56126

  • Novartis Investigative Site

    Roma, RM, 00144

  • Novartis Investigative Site

    Torino, TO, 10126

Other trials in Italy

United Kingdom5 sites

  • Novartis Investigative Site

    Glasgow, G12 0YN

  • Novartis Investigative Site

    Gloucester, GL1 3NN

  • Novartis Investigative Site

    London, SE5 9RS

  • Novartis Investigative Site

    London, W12 0HS

  • Novartis Investigative Site

    Newport, NP20 2UB

Other trials in United Kingdom

Czechia4 sites

  • Novartis Investigative Site

    Brno, 625 00

  • Novartis Investigative Site

    Plzen Bory, 301 00

  • Novartis Investigative Site

    Prague, 100 34

  • Novartis Investigative Site

    Prague, 128 00

Other trials in Czechia

Malaysia4 sites

  • Novartis Investigative Site

    Alor Star, Kedah, 05460

  • Novartis Investigative Site

    Kuala Lumpur, 59100

  • Novartis Investigative Site

    Kuching, Sarawak, 93586

  • Novartis Investigative Site

    Petaling Jaya, Selangor, 46150

Other trials in Malaysia

Hungary3 sites

  • Novartis Investigative Site

    Budapest, 1083

  • Novartis Investigative Site

    Budapest, 1097

  • Novartis Investigative Site

    Eger, 3300

Other trials in Hungary

Singapore3 sites

  • Novartis Investigative Site

    Singapore, 119074

  • Novartis Investigative Site

    Singapore, 169608

  • Novartis Investigative Site

    Singapore, 308433

Other trials in Singapore

Turkey (Türkiye)3 sites

  • Novartis Investigative Site

    Ankara, Sihhiye-Altindag, 06230

  • Novartis Investigative Site

    Istanbul, Fatih, 34098

  • Novartis Investigative Site

    Izmir, 35100

Other trials in Turkey (Türkiye)

Canada2 sites

  • Novartis Investigative Site

    London, Ontario, N6A 5W9

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

South Korea2 sites

  • Novartis Investigative Site

    Bundang Gu, Gyeonggi-do, 13620

  • Novartis Investigative Site

    Uijeongbu-si, Gyeonggi-do, 11759

Other trials in South Korea

Jordan1 site

  • Novartis Investigative Site

    Amman, 11941

Other trials in Jordan

Netherlands1 site

  • Novartis Investigative Site

    Dordrecht, South Holland, 3318 AT

Other trials in Netherlands

Oman1 site

  • Novartis Investigative Site

    Khoudh, 123

Other trials in Oman

Slovakia1 site

  • Novartis Investigative Site

    Bratislava, 851 07

Other trials in Slovakia

South Africa1 site

  • Novartis Investigative Site

    Pretoria, Gauteng, 0181

Other trials in South Africa

Switzerland1 site

  • Novartis Investigative Site

    Geneva, 1211

Other trials in Switzerland

United Arab Emirates1 site

  • Novartis Investigative Site

    Abu Dhabi

Other trials in United Arab Emirates

About this study

Official title: A Phase IIIb, Multi-center, Open-label, Randomized Study of Tolerability and Efficacy of Oral Asciminib Versus Nilotinib in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase.

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).

Read the detailed description

The study is designed to compare the tolerability of asciminib with nilotinib for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP and has 3 phases: Treatment Phase, Optional Treatment-Free Remission (TFR) Phase, and Treatment Re-initiation (TRI) Phase.

Participants were randomized in the study in a 1:1 ratio to asciminib or nilotinib. No crossover of study treatment across arms were allowed.

Randomization was stratified based on European Treatment Outcome Study (EUTOS) long-term survival (ELTS) score (low versus intermediate versus high) to help achieve a balance between the treatment arms.

An interim analysis was planned in the protocol when 46 discontinuations due to AE occurred. The purpose of the interim analysis was to allow an early assessment of the tolerability of asciminib and the goal was to continue to primary analysis regardless of the outcome of the interim analysis. Therefore, following the interim analysis, the primary analysis was performed when approximately 65 discontinuations of either study treatment due to Adverse Event (AE) occurred.

Eligible participants on both arms may choose to participate in an optional 2-year Treatment Free Remission (TFR) Phase. Participants with loss of Major Molecular Response (MMR) during TFR Phase will enter the Treatment Re-initiation (TRI) Phase. Additionally, treatment re-initiation in the TRI Phase may be based on investigator or participant decision.

Being tested
Asciminib, Nilotinib
Keywords
Asciminib, ABL001, Abelson proto-oncogene, ABL, newly diagnosed Chronic Myelogenous Leukemia, CML, Chronic Myeloid Leukemia, Chronic Myelocytic Leukemia, 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
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myeloproliferative Disorders, Philadelphia Chromosome, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AsciminibDrug

    Also called ABL001

    Asciminib 80 mg QD administered under fasting conditions.

  • NilotinibDrug

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

Study groups in NCT05456191
Study groupRoleWhat they receive
AsciminibExperimentalParticipants received asciminib 80 mg once a day (QD).
Receives: Drug: Asciminib
NilotinibActive comparatorParticipants will receive nilotinib 300 mg BID
Receives: Drug: Nilotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to Discontinuation of Study Treatment Due to Adverse Event (TTDAE) (From Interim Analysis)

    TTDAE is defined as the interval from the date of first study treatment administration to the date of discontinuation of study treatment due to an adverse event (AE). The comparison between the asciminib and nilotinib treatment arms is performed using a cause-specific hazard model, in which discontinuations due to AE are considered the event of interest and discontinuations for reasons other than AE are treated as competing risks. The number of participants who discontinued study treatment due to AE within the specified timeframe is presented in the results table. The formal comparison between treatment arms is performed using a cause-specific hazard model, and the corresponding hazard ratio, confidence interval, and p-value are provided in the Statistical Analysis section. The TTDAE endpoint is event-driven by counting how many participants have experienced treatment discontinuations due to AE.

    Measured: From date of first dose to date of treatment discontinuation due to AE, assessed after 50 events had occurred, about 2 years since first patient first visit (FPFV).

  2. Time to Discontinuation of Study Treatment Due to Adverse Event (TTDAE) (From Primary Analysis)

    TTDAE is defined as the interval from the date of first study treatment administration to the date of discontinuation of study treatment due to an adverse event (AE). The comparison between the asciminib and nilotinib treatment arms is performed using a cause-specific hazard model, in which discontinuations due to AE are considered the event of interest and discontinuations for reasons other than AE are treated as competing risks. The number of participants who discontinued study treatment due to AE within the specified timeframe is presented in the results table. The formal comparison between treatment arms is performed using a cause-specific hazard model, and the corresponding hazard ratio, confidence interval, and p-value are provided in the Statistical Analysis section. The TTDAE endpoint is event-driven by counting how many participants have experienced treatment discontinuations due to AE.

    Measured: From date of first dose to date of treatment discontinuation due to AE, assessed after 67 events had occurred, about 2.5 years since first patient first visit (FPFV),

Secondary outcomes (23)

  1. Percentage of Participants With Major Molecular Response (MMR) at Scheduled Data Collection Time Points

    MMR will be assessed using fusion gene of the BCR and ABL genes (BCR-ABL) transcript levels measured by realtime quantitative polymerase chain reaction.

    The percentage of participants with MMR at each time point will be assessed.

    Measured: approximately 7.5 years

  2. Percentage of Participants With Major Molecular Response (MMR) by Scheduled Data Collection Time Points

    MMR will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

    The percentage of participants who meet the criteria for having achieved the endpoint (MMR) at or before the specified visit will be calculated.

    Measured: approximately 7.5 years

  3. Percentage of Participants With MR4.0 at Scheduled Data Collection Time Points

    MR4.0 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

    The percentage of participants with MR4.0 at each time point will be assessed.

    Measured: approximately 7.5 years

  4. Percentage of Participants With MR4.0 by Scheduled Data Collection Time Points

    MR4.0 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

    The percentage of participants who meet the criteria for having achieved the endpoint (MR4.0) at or before the specified visit will be calculated

    Measured: approximately 7.5 years

  5. Percentage of Participants With MR4.5 at Scheduled Data Collection Time Points

    MR4.5 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

    The percentage of participants with MR4.5 at each time point will be assessed.

    Measured: approximately 7.5 years

  6. Percentage of Participants With MR4.5 by Scheduled Data Collection Time Points

    MR4.5 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.

    The percentage of participants who meet the criteria for having achieved the endpoint (MR4.5) at or before the specified visit will be calculated

    Measured: approximately 7.5 years

  7. Percentage of Participants With Complete Hematological Response (CHR) at Scheduled Data Collection Time Points

    Hematologic response will be assessed by complete blood count and physical examination at each visit.

    The percentage of participants with CHR at each time point will be assessed.

    Measured: approximately 7.5 years

  8. Percentage of Participants With Complete Hematological Response (CHR) by Scheduled Data Collection Time Points

    Hematologic response will be assessed by complete blood count and physical examination at each visit.

    The percentage of participants who meet the criteria for having achieved the endpoint (CHR) at or before the specified visit will be calculated

    Measured: approximately 7.5 years

  9. Percentage of Participants With BCR::ABL1 Ratio ≤1% at Scheduled Data Collection Time Points

    The percentage of participants who meet the criteria for having achieved BCR::ABL1 ratio ≤1% at the specified visit will be calculated

    Measured: approximately 7.5 years

  10. Percentage of Participants With BCR::ABL1 Ratio ≤1% by Scheduled Data Collection Timepoints

    The percentage of participants who meet the criteria for having achieved BCR::ABL1 ratio ≤1% at or before the specified visit will be calculated

    Measured: approximately 7.5 years

  11. Duration of MMR

    Duration of MMR is defined as the time between the date of the first documented achievement MMR and the earliest date of loss of MMR, treatment failure, progression to AP/BC, or CML-related death.

    Measured: approximately 7.5 years

  12. Duration of MR4.0

    Duration of MR4.0 is defined as the time between the date of the first documented achievement MR4 and the earliest date of loss of MR4, treatment failure, progression to AP/BC, or CML-related death

    Measured: approximately 7.5 years

  13. Duration of MR4.5

    Duration of MR4.5 is defined as the time between the date of the first documented achievement MR4.5 and the earliest date of loss of MR4.5, treatment failure, progression to AP/BC, or CML-related death.

    Measured: approximately 7.5 years

  14. Time to First MMR

    Time to first MMR is defined as the time from the date of randomization to the date of the first documented occurrence of MMR.

    Measured: approximately 7.5 years

  15. Time to First MR4.0

    Time to first MR4.0 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.

    Measured: approximately 7.5 years

  16. Time to First MR4.5

    Time to first MR4.5 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.5.

    Measured: approximately 7.5 years

  17. Time to Treatment Failure (TTF).

    TTF is defined as the time from date of randomization to the first/earliest documented date of any of the following events:

    • Treatment failure per European leukemia network (ELN) criteria,
    • Confirmed loss of MMR (in 2 consecutive tests) at any time while on study treatment,
    • Discontinuation from study treatment due to any reason

    Measured: approximately 7.5 years

  18. Event Free Survival (EFS)

    EFS is defined as the time from the date of the first dose of study treatment to the earliest occurrence of treatment failure, confirmed lost of MMR, discontinuation due to AE, progression to AP/BC, and death from any cause.

    Measured: approximately 7.5 years

  19. Progression Free Survival (PFS).

    PFS is defined as the time from the date of randomization to the earliest occurrence of progression to AP/BC or death from any cause.

    Measured: approximately 7.5 years

  20. Overall Survival (OS).

    OS is defined as the time from the date of randomization to the date of death from any cause.

    Measured: approximately 7.5 years

  21. Time to Treatment Discontinuation (TTD) Due to Selected Reasons

    TTD is the time from the date of first dose of study treatment to the date of discontinuation of study treatment due to lack of efficacy, treatment failure, disease progression, suboptimal response or death

    Measured: approximately 7.5 years

  22. Change From Baseline in Overall Scores and Individual Scales of the European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30)

    Change from baseline in Overall Scores and individual domains of the EORTC QLQ-C30. The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures based on the participant's experience over the past week. These include five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale.

    Measured: approximately 7.5 years

  23. Change From Baseline in Overall Scores and Individual Scales of the European Organization for Research and Treatment of Cancer CML Module (EORTC QLQ-CML24)

    Change from baseline in Overall Scores and individual domains of the EORTC QLQ-CML24. The EORTC QLQ-CML24 assesses specific concepts relevant to the experience of patients with CML. The QLQ-CML24 has 24 items which assess symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life based on the participant's experience over the past week.

    Measured: approximately 7.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2022
  2. Study start21 Nov 2022
  3. Primary completion15 May 2025
  4. Study completion7 Jul 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
568 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05456191
Sponsor's protocol ID
CABL001J12302
Other IDs
2024-510947-71-00
Acronym
ASC4START
Status last verified
Aug 2026
First submitted
11 Jul 2022
Last updated
26 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Asciminib and Nilotinib in people with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 119 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 119 sites in Germany, France, United States, Romania, Argentina and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Discontinuation of Study Treatment Due to Adverse Event (TTDAE) (From Interim Analysis) (time frame: From date of first dose to date of treatment discontinuation due to AE, assessed after 50 events had occurred, about 2 years since first patient first visit (FPFV).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05456191.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

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