Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

NCT05143840 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HJKC3-0004CABL001AUS06T
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

Brief Summary

This study is a multicenter Phase 2, non-randomized, open-label single-group frontline study administering asciminib in patients with newly diagnosed Chronic Myeloid Leukemia-Chronic Phase (CML-CP). The aim of this study is to evaluate the efficacy and safety of asciminib in newly diagnosed CML-CP. Patients will receive asciminib 80 mg orally once daily during the single asciminib phase. Response is determined by PCR (polymerase chain reaction) blood test during the study. Patients who have not achieved a response after 24 months (but no later than 36 months) of single agent asciminib will be offered the addition of a low dose tyrosine kinase inhibitor (low-TKI) namely dasatinib, imatinib, or nilotinib at the investigator's discretion. The following doses of the TKIs will be used:

1. 1.Dasatinib 50 mg daily
2. 2.Imatinib 300 mg daily
3. 3.Nilotinib 300 mg daily

Conditions

Chronic Myeloid Leukemia, Chronic Phase; Adult CML; Leukemia, Myeloid; Leukemia,Myeloid, Chronic

Keywords

Chronic Myeloid Leukemia; Adult CML; tyrosine kinase inhibitors; H. Jean Khoury Cure CML Consortium; HJKC3-0004

Outcome Measures

Primary Outcomes (2)

• Primary Outcome Measure 1: Deep Molecular Response

  The proportion of patients achieving BCR::ABL1 \<0.01% IS (MR4.0) within 12 months of treatment with single agent asciminib

  24 months

• Digital Droplet PCR

  Digital droplet PCR (ddPCR). Our Consortium work in the LAST study showed that ddPCR is more sensitive than conventional PCR and is very important in predicting TFR in detecting BCR::ABL1 in cases without detectable disease by conventional PCR29. Thus, samples taken for BCR::ABL1 monitoring in this trial will also be tested by ddPCR using the Bio-Rad platform. This will allow for a head to head comparison of these two methods.

  2 years

Secondary Outcomes (9)

• The rates of BCR::ABL1 IS ≤10%, ≤1% (MR2), ≤0.1% (MMR), ≤0.01% (MR4), and ≤0.0032% MR4.5

  2 years

• Time to complete hematological response.

  2 years

• Duration of MR1, MR2, MMR, MR4.0, MR4.5, and undetectable BCR::ABL1.

  2 years

• FFS, TFS, EFS, and OS

  2 years

• Adverse Events

  2 years

Other Outcomes (8)

• Adverse Events when low TKI added

  2 years

• Loss of MMR

  2 years

• Evaluate the rates of BCR::ABL1

  2 years

Study Arms (3)

Single Agent Asciminib Arm

EXPERIMENTAL

Asciminib 80mg Asciminib will be taken orally once a day starting cycle 1 day 1 for up to 24 months during the single agent asciminib phase. Patients will receive asciminib orally 80mg orally once a day starting cycle 1 day 1 for up to 24 months during the single agent asciminib phase.

Drug: Single Agent Asciminib

Adding Low TKI

EXPERIMENTAL

TKI should begin within 28-days of obtaining central eligibility confirmation. This phase II trial will use single agent asciminib 80 mg PO daily during the single agent asciminib phase. All eligible subjects will begin asciminib on cycle 1 day 1 of this trial. Low dose tyrosine kinase inhibitor (lowTKI) (dasatinib 50 mg daily or imatinib 300 mg daily or nilotinib 300 mg daily) at investigators discretion, may be added to asciminib in the following situations: * Patients who have treatment failure at any time based on ELN criteria (Appendix 7) * Patients who have a warning response after 12 months of single agent asciminib based on ELN criteria (Appendix 7) * Patients who have not achieved MR4.5 after 24 months, but no later than 36 months, of single agent asciminib.

Combination Product: Low TKI

Elective treatment free remission arm:

EXPERIMENTAL

.Elective treatment free remission arm: Once central eligibility has been obtained the patient should discontinue asciminib and if applicable lowTKI within 14 days.

Other: Elective Free Treatment

Interventions

Single Agent Asciminib DRUG

taken orally once a day starting cycle 1 day 1 for up to 24 months during the single agent asciminib phase. Asciminib is a potent allosteric inhibitor of BCR::ABL1.

Also known as: ABL001

Single Agent Asciminib Arm

Low TKI COMBINATION_PRODUCT

Low dose tyrosine kinase inhibitor (lowTKI) (dasatinib 50 mg daily or imatinib 300 mg daily or nilotinib 300 mg daily) at investigators discretion, may be added to asciminib in the following situations: * Patients who have treatment failure at any time based on ELN criteria (Appendix 7) * Patients who have a warning response after 12 months of single agent asciminib based on ELN criteria (Appendix 7) * Patients who have not achieved MR4.5 after 24 months, but no later than 36 months, of single agent asciminib.

Adding Low TKI

Elective Free Treatment OTHER

Once central eligibility has been obtained the patient should discontinue asciminib and if applicable lowTKI within 14 days.

Elective treatment free remission arm:

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years old
• Willing and able to give informed consent
• Newly diagnosed with CML in chronic phase within 6 months from confirmed diagnosis via bone marrow biopsy/aspirate and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR::ABL1 protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility.
• Minimal prior CML therapy with a TKI for less than or equal to 30 days. Treatment with hydroxyurea, busulfan, anagrelide or other non-specific chemotherapy agents is allowed with no time restrictions within the eligible time from diagnosis.
• ECOG performance status 0-2 (appendix 1)
• Adequate organ function:
• AST and ALT \< 3 times the institutional upper limit of normal (ULN)
• eGFR ≥ 30 mL/min as calculated using the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine equation (https://www.kidney.org/professionals/kdoqi/gfr\_calculator)
• Total bilirubin \< 1.5 times the institutional ULN or \< 3.0 x the institutional ULN with Gilbert Syndrome (unless direct bilirubin is within normal limits)
• Adequately controlled blood pressure, defined as systolic blood pressure of \<140 mmHq and diastolic of \<90 mmHg, at the time of enrollment.
• Lipase ≤ 1.5 x ULN. For lipase \> ULN - ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis.
• Creatine phosphokinase \< 2.5 x ULN
• Female patients must meet one of the following:
• Postmenopausal for at least one year before the screening visit,
• Surgically sterile

You may not qualify if:

• Patients with accelerated or blast phase CML (refer to appendix 4)
• Active second malignancy requiring active treatment
• History of recent (within 12 months) acute pancreatitis or chronic pancreatitis
• Subjects who have previously received treatment with asciminib.
• Subjects with PLT count \< 50,000 mm3 or ANC of \< 500 mm3 or Hemoglobin \< 8 g/dL
• Cardiac or cardiac repolarization abnormality, including any of the following:
• History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
• 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)
• QTcF at screening greater than or equal to 450 msec (male patients), greater than or equal to 460 msec (female patients) unless patient has a pacemaker
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• i. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii. Concomitant medication(s) with a "Known risk of Torsades de Pointes" per wwwcrediblemeds.org/ that cannot be discontinued or replace 7 days prior to starting study drug by safe alternative medication.
• iii. Inability to determine the QTcF interval
• Pregnant or lactating
• Taking a strong inhibitors or inducers of CYP3A4 or CYP3A4 substrates with narrow therapeutic index (refer to appendix 6) at time of enrollment
• Unable to comply with lab appointment schedule and PRO assessments

Sponsors & Collaborators

• Augusta University: lead
• H. Jean Khoury Cure CML Consortium: collaborator

Study Sites (7)

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib

Condition Hierarchy (Ancestors)

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

Study Officials

• Jorge Cortes, MD

  Augusta University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Sonnenberg

CONTACT

910-619-2597; jsonnenberg@augusta.edu

GCC Clinical Trials Office

CONTACT

706-721-2505; Cancer_Center_Trials@augusta.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single group frontline asciminib

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: December 3, 2021
• Study Start: April 22, 2022
• Primary Completion (Estimated): February 1, 2032
• Study Completion (Estimated): February 1, 2032
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

US (7)