An Exploratory Phase 1b Open-label Multi-arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination With Anti-Leukemia Agents in Subjects With Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 22
- 试验地点
- 14
- 主要终点
- Dose Limiting Toxicity (DLT)
研究概览
简要总结
CC-90009-AML-002 is an exploratory Phase 1b, open-label, multi-arm trial to evaluate the safety and efficacy of CC-90009 in combination with anti-leukemia agents in participants with acute myeloid leukemia (AML).
详细描述
Study CC-90009-AML-002 is an open-label, multi-arm, parallel multi-cohort, multicenter, Phase 1b study to determine the safety, tolerability, PK, and efficacy of CC 90009 in combination with anti-leukemia agents used for the treatment of AML. CC 90009 will be given as a combination therapy to subjects with newly diagnosed (ND) or relapsed or refractory (R/R) AML.
The dose and schedule finding part (Part A) of the study will evaluate the safety, PK and PD data, and preliminary efficacy information and determine the Part B dose and schedule for each arm.
The expansion part (Part B) of the study will further evaluate the safety and efficacy of the CC-90009 containing combination at or below the maximum tolerated dose (MTD) in the selected cohorts in order to determine the recommended Phase 2 dose (RP2D) for subjects with AML.
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
- •Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Arm A (CC-90009 + venetoclax/azacitidine):
- •Part A: Newly diagnosed AML with poor/adverse risk genetic abnormalities and is either ≥ 75 years of age or is ineligible for intensive chemotherapy OR
- •Part A: Primary Refractory AML, or AML in first relapse, and is ≥ 18 years of age
- •Part B: Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible
- •Arm B (CC-90009 + gilteritinib):
- •Subject is ≥ 18 years of age.
- •Fms-like tyrosine kinase 3 (FLT3) mutation positive.
- •Gilteritinib treatment naïve
- •Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
- •Subject must have the following screening laboratory values:
- •Total White Blood Cell count (WBC) < 25 x 10^9/L prior to study treatments. Treatment with hydroxyurea to achieve this level is allowed.
- •Selected electrolytes within normal limits or correctable with supplements.
- •Participant must have adequate liver function as demonstrated by: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) and bilirubin ≤ 1.5 x ULN
- •Participant has adequate renal function as demonstrated by an estimated serum creatinine clearance of ≥ 30 mL/min.
- •Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.
排除标准
- •Subject with acute promyelocytic leukemia (APL)
- •Subject has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment
- •Patients with prior autologous hematopoietic stem cell transplant (HSCT) who, in the investigator's judgment, have not fully recovered from the effects of the last transplant (eg, transplant related side effects)
- •Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing
- •Subject on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of topical steroids for ongoing skin or ocular GVHD is permitted
- •Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2
- •Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.
- •Disorders or conditions disrupting normal calcium homeostasis or preventing calcium supplementation.
- •Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- •Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
- •Complete left bundle branch or bifascicular block.
- •Congenital long QT syndrome.
- •Persistent or clinically meaningful ventricular arrhythmias.
- •QTcF ≥ 470 ms (Arm A) or > 450 ms (Arm B) on Screening electrocardiogram (ECG)
- •Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study treatments or unstable arrhythmia.
- •Cardiovascular disability status of New York Heart Association Class ≥
- •Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
- •Subject is a pregnant or lactating female
- •Additional exclusion criteria based on combination agent:
- •a. For Combination Arm A (venetoclax/azacitidine):
- •Received strong or moderate CYP3A inhibitors or inducers or P-gp inhibitors within 7 days prior to initiation of first venetoclax dose.
- •Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or Star fruit within 3 days prior to first venetoclax dose through last dose of venetoclax.
- •Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D
- •a. Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the participant at a higher risk of receiving study treatment.
- •Previous SARS-CoV-2 vaccine within 14 days of C1D1.
研究组 & 干预措施
CC-90009 in combination with venetoclax and azacitidine
CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD.
Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle.
干预措施: CC-90009 (Drug)
CC-90009 in combination with venetoclax and azacitidine
CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD.
Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle.
干预措施: Venetoclax (Drug)
CC-90009 in combination with venetoclax and azacitidine
CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD.
Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle.
干预措施: Azacitidine (Drug)
CC-90009 in combination with gilteritinib
CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD.
干预措施: Gilteritinib (Drug)
结局指标
主要结局
Dose Limiting Toxicity (DLT)
时间窗: Up to 28 days
Number of participants with a DLT
Adverse Events (AEs)
时间窗: Up to 28 days after last dose of study drug.
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology.
次要结局
- Objective Response Rate (ORR)(Up to 3 years)
- Time to Remission(Up to 3 years)
- Duration of Remission(Up to 3 years)
- Pharmacokinetics - t1/2(Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3))
- Complete Remission Rate (CRR),(Up to 3 years)
- Progression Free Survival (PFS)(Up to 3 years)
- Overall Survival (OS)(Up to 3 years)
- Pharmacokinetics - Cmax(Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3))
- Pharmacokinetics - AUC24(Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3))