Protocol Number: HJKC3-0003. Treatment Free Remission After Asciminib Based Therapy in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients Who Relapsed After a Prior Attempt at TKI Discontinuation

NCT04838041 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00040685
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 4

Brief Summary

This is a single arm phase II study that will enroll a minimum of 47 subjects with a maximum of 51. All patients will have a confirmed diagnosis of chronic phase chronic myeloid Leukemia and must have previously attempted to discontinue Tyrosine Kinase inhibitors (TKI). All patients must have restarted the same TKI they were on prior to discontinuation at the time of relapse in order to be eligible for this trial.

Conditions

Chronic Phase Chronic Myelogenous Leukemia

Keywords

chronic myelogenous leukemia; treatment-free remission; tyrosine kinase inhibitors; H. Jean Khoury Cure CML Consortium; Asciminib

Outcome Measures

Primary Outcomes (1)

• One-year "second" treatment-free remission.

  This will be measured by the number of subjects who achieve one-year treatment-free remission after 12 months of asciminib based therapy. These subjects have previously failed a first treatment free remission attempt.

  1 year after stopping treatment

Study Arms (4)

Asciminib 40 mg PO daily plus imatinib (maximum dose of 400 mg PO once daily)

EXPERIMENTAL

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

Drug: Asciminib 40 MG; Drug: Imatinib

Asciminib 40 mg twice daily plus nilotinib (maximum dose of 300 mg twice daily)

EXPERIMENTAL

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

Drug: Asciminib 40 MG Twice Daily; Drug: Nilotinib

Asciminib 80 mg daily plus dasatinib (maximum dose of 100 mg PO once daily)

EXPERIMENTAL

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

Drug: Asciminib 80 MG daily; Drug: Dasatinib

Asciminib 80 mg PO daily taken alone

EXPERIMENTAL

All eligible patients will begin asciminib plus/minus TKI on cycle 1 day 1 of the consolidation phase. They will continue therapy for a total of 12 cycles (minimum of 12 months). Each cycle will be \~28 days. At the end of 12 cycles, asciminib plus/minus TKI will be discontinued in patients who continue to satisfy the requirements for TFR attempt.

Drug: Asciminib 80 MG daily

Interventions

Asciminib 40 MG DRUG

40 mg by mouth (PO) when used with imatinib.

Also known as: ABL001

Asciminib 40 mg PO daily plus imatinib (maximum dose of 400 mg PO once daily)

Asciminib 40 MG Twice Daily DRUG

40 mg twice daily when used with nilotinib.

Also known as: ABL001

Asciminib 40 mg twice daily plus nilotinib (maximum dose of 300 mg twice daily)

Asciminib 80 MG daily DRUG

80 mg daily when used with dasatinib or taken alone.

Also known as: ABL001

Asciminib 80 mg PO daily taken alone; Asciminib 80 mg daily plus dasatinib (maximum dose of 100 mg PO once daily)

Imatinib DRUG

Maximum dose of 400 mg PO once daily.

Also known as: Gleevec

Asciminib 40 mg PO daily plus imatinib (maximum dose of 400 mg PO once daily)

Nilotinib DRUG

Maximum dose of 300 mg twice daily.

Also known as: TASIGNA

Asciminib 40 mg twice daily plus nilotinib (maximum dose of 300 mg twice daily)

Dasatinib DRUG

Maximum dose of 100 mg PO once daily.

Also known as: Sprycel

Asciminib 80 mg daily plus dasatinib (maximum dose of 100 mg PO once daily)

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.
• Diagnosed with chronic myelogenous leukemia (CML) in chronic phase without BCR::ABL1 \^T315I 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.
• Must have a documented history of attempting only one prior TKI discontinuation under the guidance of a treating physician. TKI includes dasatinib, imatinib or nilotinib.
• Must have met all the following criteria prior to first attempt to discontinue their TKI:
• Stable molecular response (MR4; \< 0.01% IS) for \> 2 years (with allowance for a two-week variance), as documented on at least four tests, performed at least three months apart (e.g., If a patient has had \>4 PCR tests performed during the two years leading up to their initial TKI discontinuation, any value between 0.01 and 0.05% IS is considered a stable result, however, at least four tests must be \< 0.01% IS. If any results are \>0.05% IS, tests must have been repeated within one month and be less than 0.01% IS and stable.
• Treatment with one of the following FDA approved TKIs; imatinib, dasatinib, nilotinib at any dose for a minimum of approximately three years (allowance of a four-week variance) prior to discontinuing TKIs.
• Has been on any number of TKIs, but has not been resistant to any TKI (changes made for intolerance are allowed).
• Must have relapsed (defined as loss of major molecular response (MMR), RQ-PCR for BCR::ABL1 \>0.1% IS after first attempted TKI discontinuation.
• After first failed TFR attempt, must have a minimum duration of one year of retreatment with TKI, and must plan to remain on that TKI or switch to asciminib for a minimum of 12 months during the consolidation treatment phase.
• Current TKI must be the same as the TKI being taken prior to the initial TFR attempt (e.g., if patient is on imatinib prior to first TFR attempt, they should be on imatinib at time of enrollment on this study).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
• Must have a RQ-PCR for BCR::ABL1 \< 0.0032% IS (MR4.5) reported by the trial designated central lab at the time of study enrollment.
• Lipase ≤ 1.5 x upper limit of normal (ULN). For lipase \> ULN - ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis.
• 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)

You may not qualify if:

• History of accelerated or blast phase CML.
• A 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 platelet (PLT) count \< 100 × 109/L or an absolute neutrophil count (ANC) of \< 1 × 109/L or hemoglobin \< 8 g/dL.
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≥3 times the institutional upper limit of normal.
• Total bilirubin ≥ 1.5 times the institutional upper limit of normal (unless direct bilirubin is within normal limits).
• Pregnant or lactating.
• Unable to comply with lab appointment schedule and patient-reported outcome (PRO) assessments.
• Another investigational drug within four weeks of enrollment.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol.
• Patient has undergone a prior allogeneic stem cell transplant.
• Screening 12-lead electrocardiogram (ECG) showing a baseline corrected QT interval \>480msec (patients with a pacemaker will still be eligible with QTc\>500msec).
• Known active hepatitis B infection.
• Eligibility for TFR Phase:

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• H. Jean Khoury Cure CML Consortium: collaborator

Study Sites (4)

The Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, 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, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib; Imatinib Mesylate; nilotinib; Dasatinib

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Ehab Atallah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Michael J. Mauro, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

414-805-8900; cccto@mcw.edu

Ehab Atallah, MD

CONTACT

414-805-4600; eatallah@mcw.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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: April 8, 2021
• Study Start: November 11, 2021
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)