NCT06497062

Phase II Study of Sonrotoclax Combined With Chemotherapy in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Risk-stratified Treatment of Sonrotoclax Combined With Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: a Multicenter, Phase II Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: Shanghai Jiao Tong University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This single-armed study aims to investigate the safety and efficacy of sonrotoclax in combination with intensive chemotherapy in subjects with newly diagnosed AML. Subjects will be stratified based on the genetic risk classification of 2022 European LeukemiaNet (ELN) recommendations and MRD status to receive specific consolidation therapy after the induction therapy.

Detailed description

47 subjects who meet the eligibility criteria will receive no more than 2 cycles (each cycle is 28 days) of induction therapy with sonrotoclax on day5-14 combined with the standard 3+7 intensive chemotherapy regimen (3+7 regimen) containing cytarabine, and daunorubicin or idarubicin. In cycle(C)1 of induction therapy, sonrotoclax will be administered orally once daily by a 4-day dose rump-up of 20mg on Day(D)5, 40mg on D6, 80mg on D7, and 160mg on D8-14. The first 6 subjects will be enrolled in a Safety Run-in period in C1 to assess tolerability and determine the final sonrotoclax regimen. Within 42 days or before the next cycle of therapy, if ≤1 of 6 subjects has dose-limiting toxicities (DLT), the study will be continued with the sonrotoclax dose regimen as above, and if ≥2 of 6 subjects have DLTs, the dose will be adjusted. Adjustment may include reducing the dose, shortening the duration of each cycle, or terminating the study, based on the DLTs' characteristics. Subjects who achieve a composite complete remission (CRc) after induction therapy will receive further consolidation therapy, which regimen will be decided based on the ELN risk at diagnosis and MRD status detected by MFC after induction therapy. After consolidation, subjects will receive once daily sonrotoclax orally combined with azacitidine (AZA) subcutaneously once daily alternating with AZA monotherapy every 2 cycles as maintenance therapy until unacceptable toxicity, 12 months, recurrence, death, withdrawal of informed consent, or study termination determined by investigators. This single-armed study aims to investigate the safety and efficacy of a risk-stratified regimen of sonrotoclax in combination with intensive chemotherapy in subjects with newly diagnosed AML.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	sonrotoclax	Orally once daily, on D5-14. A 4-day dose ramp-up is required for the first induction. The dosing regimen will be determined in the Safety Run-in phase. If a second induction is needed, dose ramp-up is not required. In the consolidation therapy phase, subjects in the group with favorable risk and MRD negative do not need to receive Sonrotoclax treatment, and subjects in the group with favorable risk and MRD positive, or with intermediate and adverse risk will receive sonrotoclax on D1-7 at the target dose determined in the safety run-in phase, dose ramp-up is not required. In the maintenance therapy phase, subjects will receive once daily sonrotoclax on D1-14 at the target dose determined in the safety run-in phase.
DRUG	idarubicin/daunorubicin	idarubicin: On D1-3, intravenously, 10 mg/m\^2 for subjects aged \<60 years, 6 mg/m\^2 for subjects aged ≥60 years daunorubicin: On D1-3, intravenously, 60 mg/m\^2 for subjects aged \<60 years, 40 mg/m\^2 for subjects aged ≥60 years
DRUG	Cytarabine	In induction therapy phase: intravenously, 100 mg/m\^2 on D1-7. In consolidation therapy phase: subjects with favorable-risk and MRD negative will receive cytarabine intravenously at 2 g/m\^2/q12h for those aged \<60 years, at 1g/m\^2/q12h for those ≥60 years on D1-3 or 3+7 regimen, and subjects with favorable-risk and MRD positive or intermediate or adverse-risk will receive cytarabine intravenously at 1 g/m\^2/d q12h on D1-3(in combination with sonrotoclax).
DRUG	Azacitidine	75 mg/m\^2, subcutaneously, once daily, on D1-7
PROCEDURE	allo-HSCT	Per standard of procedure

Timeline

• Start date: 2024-09-04
• Primary completion: 2027-10-31
• Completion: 2028-06-30
• First posted: 2024-07-11
• Last updated: 2024-07-11

Locations

1 site across 1 country: China