Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.
NCT Number: NCT06514534
Acronym: ASC4TARGET
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Chronic Myeloid Leukemia (CML)
Interventions: DRUG: ABL001/Asciminib
Sponsor: Novartis Pharmaceuticals
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 20
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-02
Completion Date: 2028-12-01

Summary:
The objective of this Phase II study is to assess the potential of asciminib in managing CML-CP or CML-AP in patient carrying the T315I mutation. The presence of this mutation introduces treatment difficulties due to the limited available options. The study seeks to collect additional data on the effectiveness and safety of asciminib for these patients. By determining the drug's capacity to manage the disease and enhance patients outcomes, the study is designed to fill the unmet medical need and potentially offer a new therapeutic path for patients at a treatment deadlock.

Primary Outcome Measures: Rate of BCR::ABL1 (Breakpoint Cluster Region Gene::Abelson proto-oncogene) IS (International Scale) ≤ 1% [MR2 (Molecular Response 2)], Evaluation of asciminib efficacy : proportion of patients with MR2 (BCR::ABL1 IS ≤1%) level of response at 12 months., Month 12
Secondary Outcome Measures: Kinetics of response: BCR::ABL1 IS (MR2, MMR, MR4.0, MR4.5, undetectable MR4.5), Proportion of patients achieving the response levels (MR2, MMR, MR4.0, MR4.5, undetectable MR4.5), At 3, 6, 9, 12, 18 and 24 months|Estimate response to treatment MR2 at 12 months in participants with BCR::ABL1 IS > 1% at treatment initiation or maintenance of MR2 at 12 months in participants with MR2 at treatment initiation, Proportion of patients with MR2 level of response (BCR::ABL1 IS ≤ 1%) in participants without MR2 at treatment initiation or maintenance of MR2 at 12 months in participants with MR2 at treatment initiation., At 12 months|Time to Major Molecular Response (MMR) (for participants not in MMR at treatment initiation), Major Molecular Response (MMR) criteria is defined as a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to the standardized Baseline equivalent to ≤ 0.1 % BCR::ABL1 % by international scale as measured by RQ-PCR, confirmed by duplicate analysis of the same sample., up to 24 months|Duration of MMR, MMR criteria is defined as a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to the standardized Baseline equivalent to ≤ 0.1 % BCR::ABL1 % by international scale as measured by RQ-PCR, confirmed by duplicate analysis of the same sample., up to 24 months|Time to Molecular Response 2 (MR2) (for participants not in MR2 at treatment initiation), MR2 criteria is defined as a ≥ 2.0 log reduction in BCR::ABL1 transcripts compared to the standardized Baseline equivalent to ≤ 1 % BCR::ABL1 % by international scale as measured by RQ-PCR, confirmed by duplicate analysis of the same sample., up to 24 months|Duration of MR2, MR2 criteria is defined as a ≥ 2.0 log reduction in BCR::ABL1 transcripts compared to the standardized Baseline equivalent to ≤ 1 % BCR::ABL1 % by international scale as measured by RQ-PCR, confirmed by duplicate analysis of the same sample, up to 24 months|Overall survival (OS), Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause. If a patient is not known to have died, then OS will be censored at the latest date the patient was known to be alive (on or before the cut-off date)., up to 24 months|Progression Free Survival (PFS), Progression Free Survival (PFS) is defined as time from the first dose of study medication to earliest occurrence of documented disease progression to AP/BC (depending on CML phase at asciminib initiation: CP or AP) or death due to any cause, whichever occurs first., up to 24 months|Event Free Survival (EFS), Event Free Survival is defined as time from the first dose of study medication to an event which may include:

* Treatment failure
* Confirmed loss of MR2 at any time while on study treatment,
* Discontinuation of study treatment due to AE,
* Progression to AP/BC (including progressions observed during the survival follow up period),
* Death from any cause (including deaths observed during the survival follow-up period)., up to 24 months|Failure Free Survival (FFS), Failure Free Survival (FFS) is defined as time from the first dose of study medication to a failure event which may include:

* Treatment failure
* Confirmed loss of MR2 at any time while on study treatment,
* Discontinuation of study treatment due to AE., up to 24 months|Adverse events (AEs) and Serious Adverse events (SAEs), Description/severity (grade of severity) of AE (all AE, serious or not serious AE, related and not related AE), and number of patients who discontinued the treatment due to AE., up to 24 months|Deaths and reasons for death, To evaluate the safety and tolerability profile of asciminib., up to 24 months