Phase Ib/II Study of the Glutaminase Inhibitor CB-839 in Combination With Azacitidine in Patients With Advanced Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of Participants With a Response
研究概览
简要总结
This phase I/II trial studies the side effects of glutaminase inhibitor CB-839 in combination with azacitidine in treating patients with myelodysplastic syndrome that has spread to other places in the body. Glutaminase inhibitor CB-839 and azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety, tolerability and clinical activity of glutaminase inhibitor CB-839 (CB-839) in combination with azacitidine (AZA) for patients with advanced myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
I. To explore the pharmacokinetics (PK) of CB-839 in combination with AZA. II. To explore the pharmacodynamics (PDn) of CB-839 in combination with AZA. III. To assess overall survival, event-free survival and duration of response of CB-839 in combination with AZA.
OUTLINE:
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
- •Signed, informed consent must be obtained prior to any study specific procedures
- •Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts (RAEB)-T (acute myeloid leukemia [AML] with 20-30% blasts and multilineage dysplasia by French-American-British [FAB] criteria) by World Health Organization (WHO) and chronic myelomonocytic leukemia (CMML) are eligible
- •Subjects with high-risk MDS (i.e. International Prognostic Scoring System [IPSS] Intermediate-2 or high-risk; or R-IPSS high or very-high risk). Patients with Intermediate-1 risk by IPSS or Intermediate risk by R-IPSS and with IDH1 or IDH2, or high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
- •Subjects with prior hypomethylating agent therapy exposure may be eligible based on discussion with the principal investigator (PI)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Serum bilirubin =< 2 x the upper limit of normal (ULN) (except for patients with Gilbert's disease)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3 x the laboratory ULN
- •Creatinine clearance > 30 mL/min based on the Cockcroft-Gault equation
- •Able to understand and voluntarily sign a written informed consent, and willing and able to comply with protocol requirements
- •Resolution of all treatment-related, non-hematological toxicities, except alopecia, from any previous cancer therapy to < grade 1 prior to the first dose of study treatment
- •Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days of the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>= 45 years old and without menses for >= 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential
排除标准
- •Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
- •Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- •Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
- •Clinically significant gastrointestinal conditions or disorders that may interfere with study drug absorption, including prior gastrectomy
- •Patients with known active central nervous system (CNS) disease, including leptomeningeal involvement
- •Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last 6 months
- •Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baseline)
- •Nursing or pregnant women
- •Subjects with known hypersensitivity to study drugs or their excipients
研究组 & 干预措施
Treatment (glutaminase inhibitor CB-839, azacitidine)
Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28 and azacitidine SC or IV over 10-40 minutes on days 1-7.
干预措施: Azacitidine (Drug)
Treatment (glutaminase inhibitor CB-839, azacitidine)
Patients receive glutaminase inhibitor CB-839 PO BID on days 1-28 and azacitidine SC or IV over 10-40 minutes on days 1-7.
干预措施: Glutaminase Inhibitor CB-839 (Drug)
结局指标
主要结局
Number of Participants With a Response
时间窗: Up to 5 years, 4 months
Response is Complete Remission (CR) + Partial Remission (PR) + Marrow CR = Complete Remission (CR) is \</=5% myeloblasts with normal maturation of all cell lines\* Persistent dysplasia will be noted, Peripheral blood; hemoglobin\>/=11 g/dL, Platelets \>/= 100x10\^9/L ,Neutrophils \>/=1.0 x 10\^9/L, Blasts = 0%. Partial Remission (PR) is all CR criteria if abnormal before treatment except: Bone marrow blasts decreased by \</=50% over pretreatment but still \>5% Cellularity and morphology not relevant. Marrow CR is Bone marrow: \</= 5% meyloblasts and decreased by \>/= 50% over pretreatment† Peripheral blood: if HI responses, they will be noted in addition to marrow CR.
次要结局
未报告次要终点