A PHASE IB/II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF VISMODEGIB IN RELAPSED/REFRACTORY ACUTE MYELOGENOUS LEUKEMIA (AML) AND RELAPSED/REFRACTORY HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 38
- 主要终点
- Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8
研究概览
简要总结
This study will assess the safety and efficacy of vismodegib in patients with relapsed/refractory acute myelogenous leukemia (AML) and relapsed/refractory high-risk myelodysplastic syndrome (MDS). Patients in Cohort 1 will receive single-agent vismodegib 150 mg orally daily. In Cohort 2, patients will receive vismodegib 150 mg orally daily in combination with cytarabine 20 mg subcutaneously for 10 days.
Anticipated time on study treatment is until disease progression, intolerable toxicity, or patient withdrawal of consent.
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
- •Adult patients, >/= 18 years of age
- •Patients with documented relapsed or refractory AML, except acute promyelocytic leukemia (APL [M3 subtype]), or relapsed or refractory high-risk MDS (high-risk MDS defined as International Prognostic Scoring System (IPSS) Int-2 or high and >/= 10% blasts in bone marrow)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Negative serum pregnancy test for women of childbearing potential and use of two forms of contraception while enrolled in the study and for 7 months after the patient discontinues from study
- •Male patients with female partners of childbearing potential must agree to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 2 months after the last dose of vismodegib
- •All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade </= 2 prior to starting therapy
- •Adequate hepatic and renal function
排除标准
- •Prior treatment with a Hh pathway inhibitor
- •Prior therapy for the treatment of malignancy within 14 days of Day 1, with the exception of:
- •Hydroxyurea in patients who need to continue this agent to maintain white blood cell (WBC) counts </= 50,000/mL. Hydroxyurea must be discontinued by Day 14 of the study
- •Current evidence of active central nervous system (CNS) leukemia
- •Any other active malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix)
- •Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- •Unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication (does not include stable, lone atrial fibrillation), or myocardial infarction </= 6 months before study treatment start Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
- •Pregnant or breast-feeding women
- •Patients who refuse to potentially receive blood products and/or have a severe hypersensitivity to blood products
研究组 & 干预措施
Vismodegib
干预措施: cytarabine (Drug)
Vismodegib
干预措施: vismodegib (Drug)
结局指标
主要结局
Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8
时间窗: Week 8
CR was defined as achieved if the neutrophils count was greater than (\>) 1000 cells per microliter (µL), platelets count \>100000/µL, bone marrow blasts percentage (%) less than (\<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD). CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils \>1000 cells/µL or Not applicable \[NA\] or platelets count \>100000/µL or NA), bone marrow blasts \<5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts \<5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count \>1000 cells/µL, platelets count \>100000/µL, and \>50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts \<5% with Auer rods.
次要结局
- Duration of Overall Response (DOR)(Up to 30 days of last dose of study drug (maximum treatment duration = 225 days))
- Percentage of Participants With an Event of Death During the Study(Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days))
- Area Under the Concentration-time Curve (AUC) of Cytarabine(Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29)
- Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment(Up to 30 days of last dose of study drug (maximum treatment duration = 225 days))
- Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib(Predose on Days 8, 29 and 57)
- Median Overall Survival (OS) Time(Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days))