Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

Official Title

A Phase 2, Multi-centre, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response

Summary:

To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)

Trial Description

Primary Outcome:

• Molecular Response (MR)^4.5 rate between asciminib+imatinib and imatinib alone

Secondary Outcome:

• MR^4.5 rate at 48 weeks
• Rate of MR^4.5 at 96 weeks
• Rate of MR^4.5 by 48 and 96 weeks
• Sustained MR^4.5 from 48 weeks until 96 weeks
• Time to MR^4.5
• Difference in rate of MR^4.5 at 48 weeks
• Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax
• Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax
• Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin
• Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast
• Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau

The study is a Phase 2, multi-centre, open-label, randomized study of asciminib in two different doses (40 mg or 60 mg) in combination with imatinib 400 mg versus continued imatinib versus switch to nilotinib in subjects with chronic myeloid leukemia in chronic phase (CML-CP) who have been previously treated with imatinib first line therapy for at least one year and have not achieved deep molecular response (DMR). The eligible subjects will be randomized 1:1:1:1 to receive asciminib 60 mg QD as add-on therapy to imatinib 400 mg QD, or 40 mg QD as add-on therapy to imatinib 400 mg QD, or to continue imatinib 400 mg QD, or to switch to nilotinib 300 mg twice a day (BID). Subjects on the study will continue on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks after the last randomized subject received the first dose of treatment (the end of treatment (EOT) will be the same day for all the ongoing subjects). After the last dose received, every subject will be followed up for safety for 30 days. An interim analysis will be performed when at least 40 (50%) patients have been randomized and have been followed for their 24 weeks visit assessment or have discontinued treatment. At the time of the interim analysis, if excessive toxicity without added benefit is observed in one of the investigational arms, discontinuation of that treatment arm will be considered. The decision to discontinue an investigational arm in the study will be taken based on the risk benefit balance of the two investigational arms, and in context of the other two treatment options available for the patients in the study, namely: continue on imatinib with no potential improvement of efficacy; or switch to nilotonib with a potential to improve efficacy however, with a relatively adverse safety profile as compared to imatinib. If a decision is taken to discontinue asciminib 60 mg + imatinib treatment arm at interim analysis, subjects ongoing on that treatment arm will be provided an opportunity to continue on the study at a lower dose (asciminib 40 mg + imatinib) if the investigator considers that is in the best interest of the patient. Subjects on the imatinib continuation arm who have not achieved MR4.5 at 48 weeks may cross-over (CO) to receive the add-on treatment within 4 weeks after week 48 visit. It is planned that these subjects cross-over to receive the asciminib 60 mg combination add-on treatment, as this dose provides higher exposure. Based on the results of the interim analysis or emerging data, cross-over may be changed to the asciminib 40 mg add-on treatment. The cross-over is at the discretion of the investigator and the patient. Apart from a polymerase chain reaction (PCR) result of below MR4.5 at Week 48 visit, there are no other entry criteria for the cross-over part. Subjects on nilotinib are not allowed to cross- over to receive the add-on treatment.

View this trial on ClinicalTrials.gov