NCT04996875招募中2 期
A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 74
- 主要终点
- Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib
研究概览
简要总结
This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for Main Study:
- •Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility Committee
- •Aggressive Systemic Mastocytosis (ASM)
- •Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
- •Mast Cell Leukemia (MCL)
- •Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study).
- •ECOG (0 to 3)
- •Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
排除标准
- •for Main Study:
- •Persistent toxicity from previous therapy for AdvSM that has not resolved to ≤ Grade 1
- •Associated hematologic neoplasm requiring immediate antineoplastic therapy
- •Clinically significant cardiac disease
- •Known positivity for the FIP1L1 PDGFRA fusion. Patients with eosinophilia without detectable KIT D816V mutation must demonstrate lack of PDGFRA fusion mutation prior to enrollment
- •Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
- •History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
- •Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
- •Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening bone marrow biopsy
- •Received hematopoietic growth factor support within 14 days before the first dose of study drug
- •Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug
- •Need for treatment with high dose steroids
- •Key Inclusion Criteria for Substudy Population:
- •Rollover Cohort
- •Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving bezuclastinib
- •Demonstrated clinical benefit from bezuclastinib therapy
- •Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
- •High-Risk Cohort
- •Receiving or indicated for AHN-directed therapy.
- •Diagnosed with one of the following pathologic diagnoses of SM-AHN:
- •Myelodysplastic syndrome (MDS) that is high- or very high-risk
- •Accelerated phase myeloproliferative neoplasm (MPN)
- •MDS with excessive blasts in bone marrow or peripheral blood
- •Chronic myelomonocytic leukemia-2 (CMML-2)
- •Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits.
- •Key Exclusion Criteria for Substudy Population:
- •Diagnosis of Philadelphia chromosome-positive malignancy
- •Diagnosis of acute myeloid leukemia (AML)
- •Appropriate for allogenic hematopoietic stem cell transplantation
- •Any contraindication to selected concomitant therapy
- •Rollover Cohort: Have not demonstrated acceptable tolerability of previous bezuclastinib therapy
- •High-Risk Cohort: Previously treated with investigational therapy for AdvSM
- •High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due to treatment-related toxicity
- •High-Risk Cohort: Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening or archival bone marrow biopsy
研究组 & 干预措施
bezuclastinib
Experimental
干预措施: bezuclastinib (Drug)
结局指标
主要结局
Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib
时间窗: 18 months
Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM
时间窗: 18 months
次要结局
- Pure Pathologic Response (PPR)(18 months)
- Safety of CGT9486 as assessed by incidence of Adverse Events (AEs)(18 months)
- To determine the effects of bezuclastinib on mutation allele burden.(18 months)
- To determine the effects of bezuclastinib on serum tryptase.(18 months)
- To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.(18 months)
- Change from baseline in histopathologic findings in blood and bone marrow(18 months)
- Change in spleen and liver volume by imaging(18 months)
- Duration of Response (DOR)(18 months)
- Time to Response (TTR)(18 months)
- Progression Free Survival (PFS)(18 Months)
- Overall Survival (OS)(18 months)
研究者
研究点 (74)
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