An Escalation/Expansion, Open Label, Multicenter Study of Iadademstat and Gilteritinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+): The FRIDA Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 50
- 试验地点
- 25
- 主要终点
- Recommend Phase 2 dose (RP2D)
研究概览
简要总结
Iadademstat is being studied as a treatment for subjects with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) with FMS-like tyrosine kinase mutation (FLT3 mut+). During the trial, iadademstat will be given in combination with gilteritinib, a drug that is already approved to treat patients with FLT3-mutated R/R AML.
详细描述
This is an escalation/expansion, open label, single arm, study to investigate the safety and the RP2D of the combination of iadademstat with gilteritinib in FLT3-mutated R/R AML.
This study consists of 2 parts. A dose finding part to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and emerging activity of iadademstat and gilteritinib combination, and to determine the pharmacologically-active dose (i.e., the minimum safe and biologically active dose) of iadademstat in combination with gilteritinib, and an expansion part at the specific dose/s selected to evaluate the activity of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
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
- •Main Inclusion Criteria:
- •Diagnosis of primary AML or AML with myelodysplasia-related changes (AML-MRC)
- •Patient is in first or second relapse or has refractory disease. Patients must have had histologic verification of AML at the original diagnosis.
- •Patient must be positive for the following FLT3 mutations in bone marrow or PB: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) D835 or I836 or FLT3-ITD and specified FLT3-TKD.
- •ECOG performance status 0-2
- •Life expectancy of at least 3 months in the opinion of the investigator.
- •Normal hepatic and renal function.
- •Patient is able to swallow oral medications.
- •Female patients are postmenopausal, documented as surgically sterile, use two methods of contraception or practice true abstinence and have a negative urine pregnancy test at screening.
- •Male patients even if surgically sterilized agree to practice true abstinence or use highly effective barrier contraception.
排除标准
- •Diagnosis of acute promyelocytic leukemia.
- •Known BCR-ABL-positive leukemia.
- •AML secondary to prior chemotherapy for other neoplasms (except for MDS).
- •AML that has relapsed after or is refractory to more than 2 lines of therapy.
- •Clinically active central nervous system leukemia or prior history of NCI CTCAE Grade ≥ 3 drug-related CNS toxicity.
- •Major surgery or radiation therapy within 4 weeks prior to the first study dose.
- •Prior treatment with iadademstat is not allowed. Treatment with any other agents with KDM1A/LSD1 inhibitory activity is only allowed if treatment finalized at least 3 weeks prior to first dose on study. Previous treatment with FLT3 inhibitors is allowed in the following cases: midostaurin and sorafenib are allowed when used in first-line therapy regimen as part of induction, consolidation and/or maintenance: quizartinib and gilteritinib are allowed when used in first-line therapy regimen, as part of induction, consolidation and/or maintenance, ONLY if patients were not refractory to the drugs or if responding, relapse did not occur while on these drugs.
- •Patients not eligible to receive gilteritinib per label.
- •Prior treatment with 3 or more lines of AML therapy.
- •Treatment with any investigational products within 3 weeks prior to first dose of study treatment.
- •Uncontrolled hypertension or poorly controlled diabetes.
- •Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
- •Pregnant or lactating women.
研究组 & 干预措施
Active arm
iadademstat and gilteritinib
干预措施: Iadademstat (Drug)
Active arm
iadademstat and gilteritinib
干预措施: Gilteritinib Oral Tablet (Drug)
结局指标
主要结局
Recommend Phase 2 dose (RP2D)
时间窗: Up to 18 months
Determine the recommended Phase 2 dose (RP2D) of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R
Adverse Events (AE)
时间窗: Up to 18 months
Number of participants with Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
时间窗: Up to 18 months
Number of participants with Routine 12-lead electrocardiogram (ECG )abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Laboratory value abnormalities and/or adverse events (AE)
时间窗: Up to 18 months
Number of participants with laboratory value abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
Vital sign abnormalities and/or adverse events (AEs)
时间窗: Up to 18 months
Number of participants with vital signs abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.
iadademstat tmax
时间窗: Up to 26 days
Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.
Iadademstat Cmax
时间窗: Up to 26 days
Measurement of the highest concentration of iadademstat in the blood after a dose is given.
iadademstat Cmin
时间窗: Up to 26 days
Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.
iadademstat AUC
时间窗: Up to 26 days
Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.
iadademstat Target Engagement (TE)
时间窗: Up to 26 days
Percent of drug covalently bound to LSD1 molecule
OR rate
时间窗: Up to 18 months
Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).
次要结局
- Overall Survival (OS)(Up to 24 months)
- Overall response rate(Up to 6 months)
- Event-Free-Survival (EFS)(Up to 18 months)
- Transplantation Rate Time Frame(Up to 18 months)
- Time to Response (TTR)(Up to 6 months)
- Duration of Remission (DoR)(Up to 18 months)
- Transfusion independence rate(Up to 18 months)