Phase IIa Study to Assess Safety and Efficacy in the Relapsed/Refractory Acute Myeloid Leukemia
NCT Number: NCT06532058
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Relapsed/Refractory Acute Myeloid Leukemia (R/R-AML)
Interventions: DRUG: QHRD107 capsule，Venclexta and Azacitidine
Sponsor: Changzhou Qianhong Bio-pharma Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 53
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2023-08-10
Completion Date: 2025-05-10
Locations: Henan Cancer Hospital, Zhengzhou, Henan, 450000, China|The First People's Hospital of Changzhou, Changzhou, Jiangsu, 213000, China|Huai 'an First People's Hospital, Huaian, Jiangsu, 223300, China|Zhongda Hospital, Nanjing, Jiangsu, 210009, China|Jiangsu Province Hospital, Nanjing, Jiangsu, 210036, China|ShengJing Hospital, Shenyang, Liaoning, 110004, China|Qilu Hospital of Shandong University, Jinan, Shangdong, 250000, China|Tongren Hospital Shanghai Jiao Tong University School Of Medicine, Shanghai, Shanghai, 200000, China|Ruijin hospitol, Shanghai, Shanghai, 200025, China|Zhongnan Hospital of Wuhan University, Wuhan, 湖北, 430000, China

Summary:
The purpose of this study is to assess the safety and efficacy of QHRD107 capsule combined with Venclexta and azacitidine in the treatment of relapsed/refractory acute myeloid leukemia: a single-arm, open, multicenter Phase IIa study

Primary Outcome Measures: Maximum Tolerated Dose（Dose Escalation Phase）, Enrolled subjects performed dose climbing according to the "3+3 principle".The highest dose of DLT（Dose-Limiting Toxicity） incidence 1/6 is MTD, From screenng through to 28 day follow up period|The Compound complete response rate (CCR) and the corresponding mitigation duration (DORccr)（Dose expansion phase）, The Compound complete response rate (CCR) was defined as the percentage of participants who achieved complete remission(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery (CRi) per the European LeukemiaNet (ELN) recommendations for AML. CR was defined as bone marrow blasts \< 5%, absence of circulating blasts,absence of extramedullary disease,ANC ≥ 1.0 × 10˄9/L (1,000/µL),platelet count ≥ 100 × 10˄9/L (100 000/µL).CRh was defined as ANC ≥ 0.5 × 10˄9/L (500/µL) and platelet count ≥ 50 × 10˄9/L (50000/µL), otherwise all other CR criteria met.CRi was defined as all CR criteria except for residual neutropenia \< 1.0 × 10˄9/L (1,000/µL) or thrombocytopenia \< 100 × 10˄9/L (100 000/µL).DORccr refers to the time between the first assessment of efficacy reaching CR/CRi/CRh/MLFS/PR and the first assessment of disease recurrence or death from any cause., From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）
Secondary Outcome Measures: Safety as assessed by incidence ,severity,and causality of adverse events, The frequency and number of Adverse events, From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Plasma measurements of QHRD107, The concentration of QHRD107 was measured at 3 different doses, At the end of Cycle 1 (each cycle is 28 days)|Complete Remission Rate, The complete remission (CR) rate was defined as the percentage of participants who achieved CR per the ELN criteria for AML., From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Objective Remission Rate, The objective remission rate (ORR) was defined as the percentage of participants who achieved CR, CRh, CRi,morphologic leukemia-free state (MLFS),or partial remission (PR) per the ELN for AML.Partial remission (PR) was defined as normalization in peripheral blood neutrophil and platelet counts with at least a 50% decrease in blasts persisting in bone marrow versus baseline.MLFS was defined as bone marrow blasts \< 5%,absence of circulating blasts, absence of extramedullary disease, no hematologic recovery required., From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Duration of Remission(DOR), Duration of remission was defined as the number of days from the date of first remission (CR, CRi, or PR) per the IELN criteria for AML to the earliest recurrence or progressive disease (PD)., From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Time to first CR, CRi, CRh,MLFS,and PR, Time to first CR, CRi, CRh,MLFS,and PR was defined as the time from the start of the first dose until the first observation of CR or CRh or CRi or MLFS or PR, From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Rate of Minimal Residual Disease (MRD) Negativity, The rate of minimal residual disease (MRD) response was defined as the percentage of participants who had MRD negative status., From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Event-free lifetime, For all subjects, the time from first dosing to treatment failure, or disease recurrence, or death from any cause, whichever occurred first. Treatment ineffectiveness was defined as failure to achieve CR, CRh, CRi, or MLFS after ≤4 cycles of treatment., From the date of the patient first received treatment to the end of the fourth cycle（each cycle is 28 days）|Overall survival, Overall survival(OS) was defined as the time from the date of first treatment to the date of death, 1 year