Asciminib Treatment Optimization in ≥ 3rd Line CML-CP.

Phase 3

Active, not recruiting

• Conditions: Chronic Myelogenous Leukemia
• Interventions: Drug: ABL001 40mg BID; Drug: ABL001 80mg QD; Drug: ABL001 200mg QD

• Registration Number: NCT04948333
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of the study is to optimize the treatment of asciminib in patients with chronic myelogenous leukemia in chronic phase (CML-CP) previously treated with 2 or more Tyrosine Kinase Inhibitors (TKIs). Patients for this study will be identified based on warning criteria and resistance definition following European Leukemia Network (ELN) 2020 recommendations.

In addition, the study will investigate the use of two different posologies. For this, patients will receive asciminib 40 mg (twice-daily) BID or of 80 mg (once daily) once daily (QD).

Detailed Description

This study is an international, multi-center, non-comparative, phase IIIb, treatment optimization study of daily 80 mg asciminib (as either as 40 mg BID of asciminib or as 80 mg QD) in adult patients previously treated with 2 or more TKIs. Up to 30 patients who are intolerant to ongoing TKI treatment but in major molecular response (MMR) will also be allowed to enter the trial. Enrollment will be used to have a balance in the allocation of treatment into either asciminib 40 mg b.i.d. or 80 mg q.d. Although this trial will not be powered to compare both treatments, descriptive data from both treatment groups is expected to provide additional insight into the optimal patient management In patients not achieving MMR at 48 weeks or losing the response after the week 48 up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation. In addition, there must not be any grade 3 or 4 toxicity while on therapy, or persistent grade 2 toxicity, possibly related to asciminib and unresponsive to optimal management.

The planned duration of treatment is up to 144 weeks unless patient discontinue from treatment due to unacceptable toxicity, disease progression and/or if treatment is discontinued at the discretion of the investigator or the participant prior to week 144.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-06-28
• Study First Submitted QC: 2021-06-28
• Study First Posted: 2021-07-01
• Study Start: 2021-10-13
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-07
• Primary Completion: 2026-04-30
• Study Completion: 2026-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 199

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ABL001	ABL001 40mg BID	Participants will be treated with 80 mg of ABL001 (40 mg BID or 80mg QD). In patients not achieving MMR at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation.
ABL001	ABL001 80mg QD	Participants will be treated with 80 mg of ABL001 (40 mg BID or 80mg QD). In patients not achieving MMR at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation.
ABL001	ABL001 200mg QD	Participants will be treated with 80 mg of ABL001 (40 mg BID or 80mg QD). In patients not achieving MMR at 48 weeks or losing the response after the week 48 assessment up to week 108, asciminib dose may be escalated to 200 mg q.d. if in the investigator's opinion the patient may benefit from the escalation.

Primary Outcome Measures

Name	Time	Method
Major molecular response (MMR) rate at Week 48 for all patients with no evidence of MMR at baseline.	Week 48	To estimate the molecular response rate at week 48 of all patients (40 mg BID asciminib and 80 mg QD) with CML-CP following two or more prior TKI treatments and with no evidence of MMR at baseline.; A patient will be counted as having achieved MMR at week 48 if he/she meets the MMR criterion (BCR-ABL1 ≤ 0.1% IS) at week 48 while on study treatment and without meeting any treatment failure criteria prior to week 48.

Secondary Outcome Measures

Name	Time	Method
Rate of BCR-ABL1 ≤ 10%	Week 12, 24, 36 and 48.	To assess the rate of early responses of BCR-ABL1 ≤10%.
Rate of BCR-ABL1 ≤1%	Week 12, 24, 36 and 48.	To assess the rate of early responses of BCR-ABL1 ≤1%.
MMR rate at baseline at Week 12, 24, 36, 72, 96 and 144 for patients with no MMR at baseline.	Week 12, 24, 36, 72, 96 and 144.	To assess the rate of MMR in patients without MMR at Baseline. MMR is defined as BCR-ABL ratio ≤0.1%.
Occurrence of high-risk additional chromosomal abnormalities (ACA)	Up to 144 weeks	Occurrence of high-risk ACA to characterize the impact of additional cytogenetic abnormalities on efficacy.
Cumulative molecular response rate of BCR-ABL1 ≤ 10%.	From enrollment to end of treatment up to 144 weeks.	To assess cumulative molecular responses (BCR-ABL1 ≤ 10%) by all-time points.
Cumulative molecular response rate of BCR-ABL1 ≤1%.	From enrollment to end of treatment up to 144 weeks.	To assess cumulative molecular responses (BCR-ABL1 ≤1%) by all-time points.
Cumulative molecular response rate of MMR.	From enrollment to end of treatment up to 144 weeks.	To assess cumulative molecular responses of MMR by all-time points. MMR is defined as BCR-ABL ratio ≤0.1%.
Cumulative molecular response rate of MR4.	From enrollment to end of treatment up to 144 weeks.	To assess cumulative molecular responses of MR4 by all-time points. MR4 is defined as BCR-ABL ratio ≤0.01%.
Time to MMR.	From the date of enrollment to the date of first documented MMR, assessed up to 144 weeks	To assess the time to MMR. MMR is defined as BCR-ABL ratio ≤0.1%.
MR4 rate.	Week 12, 24, 36, 48, 72, 96 and 144.	To assess the rate of deep molecular responses MR4. MR4 is defined as BCR-ABL ratio ≤0.01%.
MR4.5 rate.	Week 12, 24, 36, 48, 72, 96 and 144.	To assess the rate of deep molecular responses MR4.5. MR4.5 is defined as BCR-ABL ratio ≤0.0032%.
Rate of complete cytogenetic response (CCyR).	Week 48 and end of treatment (up to 144 weeks)	To assess the rate of complete cytogenetic response (CCyR). CCyR is defined as 0% Ph+ metaphases in the bone marrow.
MMR rate at Week 48 for patients with MMR at baseline	Week 48.	To assess the rate of MMR for patients with MMR at Baseline. MMR is defined as BCR-ABL ratio ≤0.1%.
Cumulative molecular response rate of MR4.5.	From enrollment to end of treatment up to 144 weeks.	To assess cumulative molecular responses of MR4.5 by all-time points. MR4.5 is defined as BCR-ABL ratio ≤0.0032%.
Duration of MMR.	From the date of the first documented molecular response at MMR level to the date of first documented loss of the response level or death due to any cause, whichever occurs first, assessed up to 144 weeks.	Duration of MMR is defined as the time from the date of first documented MMR to the earliest date of loss of MMR, progression to accelerated phase (AP) or blast crisis (BC), or CML-related death.; MMR is defined as BCR-ABL ratio ≤0.1%.
Duration of MR4 without loss of MMR.	From the date of first documented MR4 without loss of MMR to the date of first documented loss of the response level or death due to any cause, whichever occurs first, assessed up to 144 weeks.	Duration of MR4 is the time from the date of the first documented MR4 without loss of MMR to the date of first documented loss of the response level or death due to any cause, whichever occurs first.; MR4 is defined as BCR-ABL ratio ≤0.01%.
Progression-Free survival (PFS)	Up to 144 weeks.	PFS is defined as the time from treatment assignment the earliest occurrence of documented disease progression to AP/BC or the date of death from any cause, assessed up to approximately 144 weeks.
Overall Survival (OS)	Up to 144 weeks.	OS is defined as the time from treatment assignment to death due to any cause during study, assessed up to 144 weeks.
Treatment failure (TTF)	Up to 144 weeks.	Time from treatment assignment to treatment failure defined as BCR-ABL1\>10%, assessed up to 144 weeks.
Change in symptom burden and interference from baseline over time according to the MDASI-CML PRO instrument.	Week 4, 12, 24, 48, 72, 96, 120 and at end of treatment (up to 144 weeks).	To evaluate patient reported outcomes and quality of life by using QoL scale. The MD Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) is a 26 item self-administered questionnaire for adult CML patients. Twenty of the items measure the severity of disease-related symptoms (symptom burden) and are scored from 0 (not present) to 10 (as bad as you can imagine) and 6 items that measure symptom interference with daily life (interference) scored from 0 (did not interfere) to 10 (interfered completely). For symptom burden, total scores range from 0 to 200 and for interference range from 0 to 60, with higher scores indicates high impact on severity of chronic myeloid leukemia-related symptoms and on impact of these symptoms on daily functioning for the patient.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇻🇳 Ho Chi Minh, Vietnam