PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML — PEARL  

Chronic Myeloid Leukemia Clinical Trial

Official title: Asciminib as Single Agent or in Combination With Nilotinib in the 1st-line Treatment of BCR-ABL1+ Chronic Myeloid Leukemia: a Randomized GIMEMA-GELMC Phase II Study PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML

Status Not yet recruiting

Clinical Trial Summary

A phase 2, interventional, randomized unblinded study will be conducted in newly diagnosed CP CML patients, to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent (arm A) or 40 mg BID in combination with nilotinib 300 mg BID (arm B).

All patients in both arm A and arm B will be treated for a minimum of 2 years (core phase). If they will have achieved a DMR (MR4), or if it will be in the interest of the patient, the treatment will be continued.

During the consolidation phase (2 years) asciminib will be continued at the same dose in both arms; in the combination arm the nilotinib dose will be reduced to 300 mg daily.

The patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment (TFR phase). The rate of TFR at 5 year (1 year after discontinuation) will be evaluated.

Clinical Trial Description

A phase 2, prospective, interventional, randomized (two arms, randomization 1:1), unblinded study will be conducted in newly diagnosed CP CML patients, to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent (arm A) or 40 mg BID in combination with nilotinib 300 mg BID (arm B).

• In the arm A, asciminib 80 mg QD will be given as single-agent. In the arm B, asciminib 80 mg QD will be started, then after 90 days asciminib will be given 40 mg BID and nilotinib 300 mg BID, or 300 mg OAD according to the presence/absence of asciminib adverse events, will be added-on in all patients. All patients in both arm A and arm B will be treated for a minimum of 2 years (core phase). If they will have achieved a DMR (MR4), or if it will be in the interest of the patient, the treatment will be continued. In both arms the study drugs may be discontinued at any time for inefficacy (failure) or safety reasons(grade 3-4 toxicity or persistent grade 2 non hematologic toxicity). However, all the patient will remain "in study" (regular follow-up information will be required). The dose adjustments for toxicity and detailed criteria for treatment discontinuation (asciminib in arm A; asciminib or nilotinib in arm B) are specified within the protocol.

• After the induction of a DMR, the residual disease will be closely monitored by Q-PCR until the fourth year (consolidation phase). During the consolidation phase (2 years) asciminib will be continued at the same dose in both arms; in the combination arm the nilotinib dose will be reduced to 300 mg daily.

• The patients maintaining a stable MR4 up to the end of the fourth year, that must include in the last year at least 3 evaluable QPCR analyses, will enter the treatment free remission (TFR) phase of the study and will discontinue the treatment (TFR phase). A single unconfirmed loss of MR4 will not preclude the possibility of treatment discontinuation. In case of confirmed loss of MR3 after discontinuation, the choice of subsequent treatment will be up to Local Investigators. The rate of TFR at 5 year (1 year after discontinuation) will be evaluated. ;

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Chronic Myeloid Leukemia, Chronic Phase
• CML, Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase

• NCT number: NCT06409936
• Study type: Interventional
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: Paola Fazi
• Phone: 0670390528
• Email: p.fazi@gimema.it
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2024
• Completion date: September 2031