A Phase 1, Open-label, Dose Finding Study of CC-90002, a Monoclonal Antibody Directed Against CD47, in Subjects With Acute Myeloid Leukemia and High-Risk Myelodsplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 28
- 试验地点
- 6
- 主要终点
- Dose-limiting Toxicity (DLT)
研究概览
简要总结
Study CC-90002-AML-001 is an open-label, Phase 1 dose escalation (Part A) and expansion (Part B), clinical study of CC-90002, administered by intravenous (IV) infusion, in subjects with relapsed and/or primary refractory AML and high-risk MDS. The study will explore escalating doses of CC-90002 using a 3 + 3 dose escalation design in Part A, followed by dose expansion in Part B.
The primary objective is to determine the safety and tolerability of CC-90002 and also to define the non-tolerated dose (NTD), the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of CC-90002.
详细描述
In both Part A and Part B, treatments will be administered in two phases starting with an induction phase followed by a maintenance phase. During the induction phase, treatments will be administered in 42-day cycles in Cycles 1 through 4. Following completion of Cycle 4 in the induction phase, subjects with non-progressive disease will enter the maintenance phase. During the maintenance phase, treatments will be administered in 28 day cycles. Subjects may continue CC-90002 for up to a maximum of 2 years (eg, induction phase Cycles 1 through 4 and maintenance phase Cycles 5 through 24) or until clinically significant disease progression, the occurrence of intolerable toxicity, or physician/subject decision to discontinue CC-90002, whichever comes first.
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
- •Men and women ≥ 18 years of age, at the time of signing the informed consent form (ICF).
- •Relapsed and/or primary refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) with subtype refractory anemia with excess blasts (RAEB)-2 defined as high or very high-risk that is recurrent or refractory, or the patient is intolerant to established therapy.
- •Subject consents to hospitalization for first (Cycle 1 Day 1) dose of CC-90002 and for 72 hours after.
- •Subject consents to serial bone marrow aspiration and biopsies as specified.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to
- •Eligible study subjects must exhibit acceptable liver, renal, and coagulation function as assessed by laboratory tests.
- •Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and for up to 8 weeks following the last dose of CC 90002.
排除标准
- •Active central nervous system (CNS) leukemia or known CNS leukemia.
- •Immediately life-threatening, severe complications of leukemia.
- •Impaired cardiac function or clinically significant cardiac diseases.
- •Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- •Prior autologous hematopoietic stem cell transplant ≤ 3 months.
- •Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤ 6 months.
- •Systemic immunosuppressive therapy post HSCT or with clinically significant graft-versus-host disease (GVHD).
- •Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks whichever is shorter.
- •Major surgery ≤ 2 weeks and recovered from any clinically significant effects of recent surgery.
- •Pregnant or nursing females.
- •Known HIV infection.
- •Known chronic hepatitis B or C (HBV/HCV) infection.
- •Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.
- •History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
- •History of concurrent second cancers requiring active, ongoing systemic treatment.
- •Subjects for whom potentially curative anticancer therapy is available.
研究组 & 干预措施
Dose escalation of CC-90002
CC-90002 by intravenous (IV) infusion on a 28 day cycle
干预措施: CC-90002 (Drug)
结局指标
主要结局
Dose-limiting Toxicity (DLT)
时间窗: Up to 26 months
Number of participants with a DLT
Non-tolerated Dose (NTD)
时间窗: Up to 26 months
The NTD is defined as the dose at which 2 or more of up to 6 evaluable subjects in a cohort experience a DLT in Cycle 1
Maximum tolerated dose (MTD)
时间窗: Up to 26 months
The MTD is defined as the last dose level(s) below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during Cycle 1.
次要结局
- Pharmacokinetics-T 1/2(Up to 35 months)
- Pharmacokinetics- CL(Up to 35 months)
- Pharmacokinetics- Vss(Up to 35 months)
- Anti-Drug Antibodies (ADAs)(Up to 35 months)
- Pharmacokinetics-Cmax(Up to 35 months)
- Pharmacokinetics-AUC(Up to 35 months)
- Pharmacokinetics-Tmax(Up to 35 months)
- Preliminary Efficacy of CC-90002(Up to 35 months)