RecruitingPhase 2ACTRN12623001338651

CML14 (ASCENDANCE) - A study to assess efficacy of combination therapy with asciminib plus low dose dasatinib in newly diagnosed chronic phase Chronic Myeloid Leukaemia (CML) with high risk genetics

CML14 (ASCENDANCE) - ASCiminib Evaluation in Newly diagnosed CML with Dasatinib to Augment response in Complex genomic Etiology

Sponsor

Australasian Leukaemia and Lymphoma Group (ALLG)

Enrollment

100 participants

Start Date

Oct 14, 2024

Study Type

Interventional

Conditions

Chronic Myeloid Leukaemia (CML)

Summary

The purpose of this trial is to assess efficacy of an induction phase of combination therapy with asciminib plus low dose dasatinib in newly diagnosed chronic phase CML (CP-CML) with high-risk genetics, with respect to achievement of major and deep molecular response. CML14 (ASCENDANCE) is a successor trial to the ALLG-sponsored CML13 (ASCEND-CML, ACTRN12620000851965). CML14 aims to further improve outcomes through the use of our NGS panel to identify AGAs, and offer these patients with AGAs frontline treatment with combination asciminib / dasatinib therapy. Who is it for? You may be eligible for this study if you are aged 18 and above and have been newly diagnosed with CP-CML. Study details Participants who choose to participate in this trial will receive treatment with asciminib monotherapy at 80mg daily for the first 4 weeks. At the end of this period, New Generation Sequencing (NGS) and cytogenetic results will be available from the central and local labs. The presence of additional genomic abnormalities (AGA) will be defined by the central lab for each case as per predefined criteria. Patients with evidence of AGAs and high risk ACAs will be assigned to the high risk cohort, and will receive combination treatment of asciminib 80mg plus dasatinib 50mg daily - All patients with high risk will receive combination therapy between months 2 to 12. - Patients who achieved Molecular Response 4 (MR4), and confirmed at a timepoint 3 months afterwards, will de-escalate to asciminib monotherapy. - Patients without MR4 at month 12 will de-escalate to asciminib monotherapy. An extension of combination therapy to the 18th month timepoint is permitted at the discretion of the investigator - Patients with intolerance to combination therapy, despite maximal supportive therapy for the same, will deescalate to asciminib monotherapy at any time All other patients (without evidence of AGAs and high risk ACAs) will be assigned to the standard risk cohort and will continue to receive asciminib 80mg daily monotherapy. - AGA negative patients will then have to achieve predetermined targets: BCR::ABL1 of less than or equal to 10 percent, at 3 & 6 months, and less than or equal to 1percent, at 12 and 18 months to continue with asciminib 80mg daily. - Patients failing to achieve these responses will have dasatinib 50mg daily added to asciminib 80mg daily. - Patients with “warning” under ELN2020 will be offered, at investigator discretion, asciminib dose escalation to 80mg twice a day. Overall treatment duration is 2 years post-enrolment. All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance. It is hoped this research will improve overall survival and molecular response achievement and minimise treatment related morbidity and mortality for CP-CML patients.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Plain Language Summary

Simplified for easier understanding

Chronic Myeloid Leukaemia (CML) is a type of blood cancer caused by a specific genetic mutation that drives uncontrolled growth of white blood cells. It is typically treatable with targeted drugs called tyrosine kinase inhibitors (TKIs). However, some newly diagnosed patients have additional genetic abnormalities (called AGAs) that make their disease higher risk and less likely to respond to standard treatment alone. The ASCENDANCE trial is testing a combination of two targeted drugs — asciminib and low-dose dasatinib — specifically for newly diagnosed CML patients with these high-risk genetic features. The trial uses genetic sequencing at diagnosis to identify who is high-risk, then tailors treatment intensity accordingly. High-risk patients receive the combination therapy; lower-risk patients receive asciminib alone. The goal is to achieve deeper and faster remissions while minimising side effects. Eligible participants are adults aged 18 and over newly diagnosed with chronic phase CML (within the past 6 months) who have not previously received more than 14 days of TKI therapy. Participants must be eligible for treatment reimbursement under the Australian PBS or New Zealand Pharmac system and must have adequate organ function.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

Asciminib is an oral-tablet available in capsule strengths of 20mg or 40mg. Both capsule strengths will be used interchangeably depending on the patient's condition. All patients will receive treat

Asciminib is an oral-tablet available in capsule strengths of 20mg or 40mg. Both capsule strengths will be used interchangeably depending on the patient's condition. All patients will receive treatment with asciminib monotherapy at 80mg daily for the first 4 weeks. • At the end of this period, New Generation Sequencing (NGS) and cytogenetic results will be available from the central and local labs. The presence of additional genomic abnormalities (AGA) will be defined by the central lab for each case as per predefined criteria. The presence of high risk Additional Cytogenetic Abnormalities (ACAs) are defined in this protocol as” duplication of Ph-positive chromosome, trisomy 8, trisomy 19, i(17q), and chromosome 3q26 abnormalities. • Patients with evidence of AGAs and high risk ACAs will be assigned to the high risk cohort, and will receive asciminib 80mg plus dasatinib 50mg daily via oral tablet. - All patients with high risk will receive combination therapy from month 2 . High risk patients are assessed for BCR-ABL1 by cytogenetics at 3, 6 and 12 months. - Patients who achieved Molecular Response 4 (MR4) at the 3 month timepoint or afterwards will de-escalate to asciminib monotherapy. Those that do not achieve MR4 at the 3 or 6 month timepoint will continue on asciminib plus dasatinib. - Patients without MR4 at month 12 will de-escalate to asciminib monotherapy. An extension of combination therapy to the 18th month timepoint is permitted at the discretion of the investigator - Patients with intolerance to combination therapy, despite maximal supportive therapy for the same, will deescalate to asciminib monotherapy at any time • All other patients will be assigned to the standard risk cohort and will continue to receive asciminib 80mg daily monotherapy. - AGA negative patients will then have to achieve predetermined targets: BCR::ABL1 of less than or equal to 10 percent, at 3 & 6 months, and less than or equal to 1percent, at 12 and 18 months. Patients failing to achieve these responses will have dasatinib 50mg daily added to asciminib 80mg daily. Patients with “warning” under ELN2020 will be offered, at investigator discretion, asciminib dose escalation to 80mg twice a day (for responses of BCR::ABL1 of less than or equal to 10percent but less than 1percent at 6 months, less than or equal to 1percent but greater than 0.1percent at 12 months, and no MR4, but achieved Major Molecular Response [MMR] at 18 months). Overall treatment duration is 2 years post-enrollment. All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.