A Phase 1 First-in-human Dose-escalation and Dose-expansion Study of BMF-219, an Oral Covalent Menin Inhibitor, in Adult Patients With Acute Leukemia (AL), Diffuse Large B-cell Lymphoma (DLBCL), Multiple Myeloma (MM), and Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 55
- 试验地点
- 41
- 主要终点
- Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2, 3 & 4)
研究概览
简要总结
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral covalent menin inhibitor, in adult patients with AML, ALL (with KMT2A/ MLL1r, NPM1 mutations), DLBCL, MM, and CLL/SLL.
详细描述
A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-219, an oral covalent menin inhibitor, in adult patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) with mixed lineage leukemia 1-rearranged (KMT2A/ MLL1r), nucleophosmin 1 (NPM1), diffuse large b-cell lymphoma (DLBCL), multiple myeloma (MM), and chronic lymphocytic lymphoma (CLL)/ small lymphocytic lymphoma (SLL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years.
- •All subjects must have histologically or pathologically confirmed diagnosis of their malignancy and/ or measurable R/ R disease, as follows:
- •Cohort 1 only: Refractory or relapsed acute leukemia defined as > 5% blasts in the bone marrow or reappearance of blasts in the peripheral blood.
- •Cohort 2 only: Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously indolent lymphoma (e.g., follicular lymphoma) with documented clinical or radiological evidence of progressive or persistent disease. At study entry, subjects must have measurable disease as per the revised criteria for response assessment of lymphoma.
- •Cohort 3 only: Measurable MM.
- •Cohort 4 only: Previously treated subjects with active CLL/SLL with meeting at least 1 of the iwCLL 2018 criteria for requiring treatment.
- •Subjects must be refractory or must have progressed on, or following discontinuation of the most recent anti-cancer therapy, with the following considerations:
- •Cohort 1 only: Have failed or are ineligible for any approved standard of care therapies, including HSCT (Hematopoietic Stem Cell Transplantation).
- •Cohort 2 only: Must have received at least 2 previous systemic regimens for the treatment of their de novo or transformed DLBCL.
- •Cohort 3 only: Must have received at least 3 anti-MM regimens including proteasome inhibitor.
- •Cohort 4 only: Must have received at least 2 prior systemic treatment regimens.
- •ECOG performance status of 0-2 and an estimated expected life expectancy of > 3 months in the opinion of the Investigator.
- •Adequate organ function.
- •Both men and women of childbearing potential or their partners must use adequate birth control measures during the course of the trial and for at least 90 days after discontinuing study treatment.
排除标准
- •Subjects who meet any of the following criteria will not be enrolled in the study (all cohorts, unless otherwise indicated):
- •Certain disease subtypes or occurrences, as follows:
- •Cohort 1: Acute promyelocytic leukemia (APL), chronic myeloid leukemia (CML) in blast crisis.
- •Cohort 2: Primary mediastinal B-cell lymphoma (PMBCL), DLBCL transformed from diseases other than indolent non-Hodgkin's Lymphoma (NHL).
- •Cohort 3: Active plasma cell leukemia, myeloma with amyloidosis, systemic light chain amyloidosis.
- •Cohort 4: Known or suspected history of Richter's transformation.
- •White Blood Count (WBC) > 50,000/μL (uncontrollable with cytoreductive therapy) (Cohort 1 only).
- •Known central nervous involvement, as follows:
- •Cohort 1: Clinically active central nervous system (CNS) leukemia. Previously controlled CNS leukemia is acceptable.
- •Cohort 2: Active CNS lymphoma or meningeal involvement.
- •Cohort 3: Active CNS MM.
- •Cohort 4: Active CNS leukemia.
- •Prior menin inhibitor therapy.
- •Known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
- •Subjects with a pre-existing disorder predisposing them to a serious or life-threatening infection.
- •An active uncontrolled acute or chronic systemic fungal, bacterial, or viral infection.
研究组 & 干预措施
Dose Escalation Phase
Experimental: ARM A:
Study participants who are not receiving a moderate or strong CYP3A4 inhibitor.
Dose Escalation Phase:
- Cohort 1: Participants with acute leukemia
- Cohort 2: Participants with diffuse large B-cell lymphoma
- Cohort 3: Participants with multiple myeloma
- Cohort 4: Participants with chronic lymphocytic leukemia/ small lymphocytic lymphoma
Participants will receive escalating dose BMF-219 orally once per day to identify the OBD/RP2D (Optimal Biologic Dose/Recommended Ph2 Dose).
Dose Expansion Phase:
Cohorts 1, 2, 3, and 4 will receive BMF-219 at the OBD/ RP2D to further assess the safety/ efficacy of the investigational drug.
干预措施: BMF-219 (Drug)
Dose Expansion
Experimental: ARM B:
Study participants who are receiving a moderate or strong CYP3A4 inhibitor.
Dose Escalation Phase:
• Cohort 1: Participants with acute leukemia will receive escalating dose BMF-219 orally to identify the OBD/ RP2D (Optimal Biologic Dose/Recommended Ph2 Dose).
Dose Expansion Phase:
Cohort 1 will receive BMF-219 at the OBD/ RP2D to further assess the safety and efficacy of the investigational drug.
干预措施: BMF-219 (Drug)
结局指标
主要结局
Determine Optimal Biologic Dose (OBD) and RP2D of BMF-219 monotherapy for (Cohorts 1, 2, 3 & 4)
时间窗: At the end of Cycle 1 (each Cycle is 28 Days in duration)
Determine Optimal Biologic Dose (OBD) and recommended Phase 2 dose (RP2D) of BMF-219 monotherapy in subjects with refractory or relapsed (R/ R) acute leukemia (Cohort 1), diffuse large B-cell lymphoma (Cohort 2), multiple myeloma (Cohort 3), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (Cohort 4).
次要结局
- Evaluate the Safety treatment-emergent TEAEs and SAEs(28 Days after last dose.)