NCT01944943终止2 期
Phase II Study of Vismodegib in Patients With Refractory or Relapsed B-cell Lymphoma or Chronic Lymphocytic Leukemia
The Lymphoma Academic Research Organisation10 个研究点 分布在 1 个国家目标入组 31 人开始时间: 2013年2月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 31
- 试验地点
- 10
- 主要终点
- The best overall response rate(ORR)
研究概览
简要总结
The purpose of this study is to determine the efficacy of Vismodegib drug in treatment of patients with relapsed or refractory B-cell lymphoma or chronic lymphocytic leukemia (CLL).
详细描述
This is a multicenter open-label phase II study.
Primary objective:
To evaluate the efficacy of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL as measured by the best overall response rate (ORR) during the treatment period.
Secondary objectives:
- To evaluate the tolerability and the safety of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL
- To evaluate the efficacy of vismodegib in patients with relapsed/refractory B-cell lymphoma and CLL by measuring the overall (OR) and complete response (CR) rate during the study period, the maximum tumor shrinkage, the duration of response, the progression-free survival (PFS) and the overall survival (OS).
- To examine the expression of GLI-1 and other Hedgehog (Hh) signalling components in the tumor specimens before and during treatment with vismodegib and corresponding efficacy in patients.
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
- •Histologically confirmed diagnosis of B-cell lymphoma (DLBCL, MCL, FL, MZL, LPL/WM, SLL or PCNSL) or CLL (Matutes score ≥4) requiring treatment that is recurrent after at least one prior therapy for which no potentially curative therapy nor better treatment option is available. Specifically, the patient should have received all treatments considered to be standards of care, including stem cell transplantation (when appropriate, if patient eligible), and agents known to have significant clinical efficacy in their disease.Patient must be eligible for tumor biopsy. Biopsy at relapse is mandatory for all patients except for PCNSL (optional) and should provide enough tumor tissue for biological tests (paraffin-embedded and frozen or RNAlater-conserved tissue).
- •Age 18 and older
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
- •Signed inform consent
- •Life expectancy ≥ 3 months
- •Patients who have received up to a maximum of 4 lines of treatment (including radiotherapy)
- •Patients must have recovered from all toxicities related to prior treatments to ≤ grade
- •Adequate Laboratory Parameters (unless abnormalities are related to underlying disease) within 28 days prior to signing informed consent, including:
- •Absolute neutrophil count (ANC) ≥ 1000/μL
- •Platelet ≥ 75,000/μL
- •Hemoglobin > 8.5 g/dL
- •Total bilirubin ≤ 1.5 x upper limit of normal (UNL)
- •Hepatic enzymes (AST, ALT) ≤ 3 x institutional ULN
- •Measurable disease:
- •Cohort 1 and 2 (DLBCL and iNHL): Bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter.
- •Cohort 3 (PCNSL): Measurable PCNSL on MRI with gadolinium enhancement (no minimal size) or, for intraocular lymphoma (IOL), measurable disease at fundoscopic examination with elevated level of IL10 (>10 pg/ml) in the acqueous humor.
- •Cohort 4 (CLL): Measurable disease assessable in the blood (lymphocytosis, cytopenia) and/or by imaging (bi-dimensionally measurable disease at CT scan with at least 2cm in their longest diameter)
- •Patient must be able to take oral medication
- •Females of childbearing potential (FCBP) must :
- •have a negative pregnancy test (serum or urine, sensitivity < or = 25IU HCG/L) within 96 hours prior to starting study drug administration.
- •Agree to use two reliable forms of contraception or to practice complete abstinence from heterosexual contact during whole treatment period and up to 7 months after discontinuation of study drug treatment
- •Male patients must agree :
- •to use a condom with female of childbearing potential or to practice complete abstinence during whole treatment period and up to 7 months after discontinuation of study drug treatment.
- •To abstain from donating semen during whole treatment period and up to 7 months after discontinuation of study drug treatment
- •For all patients receiving vismodegib (GDC-0449):
- •To agree to abstain from donating blood during the whole study and for at least 7 months after discontinuation of study drug treatment
- •To agree not to share the study medication with another person
排除标准
- •Pregnant or breastfeeding lactating females.
- •For CLL patients, clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician
- •Concomitant anti-tumor therapy (e.g., chemotherapy, corticosteroids, other targeted therapy, radiation therapy). Corticosteroids may be authorized for PCNSL only during maximum 3 weeks (before and/or at the beginning of treatment with vismodegib) at a maximum dose of 1mg/kg of prednisone or equivalent.
- •Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the study drug therapy (Day 1).
- •Patients with severe renal failure (creatinine clearance < 30 ml/min according to Cockcroft & Gault formula) and/or undergoing dialysis.
- •Note: Patients with moderate renal insufficiency (i.e. creatinine clearance ≥ 30 ml/min) may be included.
- •Uncontrolled and/or unstable concomitant disease such as infection requiring treatment with intravenous antibiotics.
- •HIV positive serology
- •Active hepatitis B or C
- •History of other disease, metabolic dysfunction, physical examination, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the study results or to expose the patient to high risk from treatment complications.
- •Patients unable to comply with the protocol requirements according to the investigator
研究组 & 干预措施
Vismodegib
Experimental
Vismodegib 150 mg will be administrated orally at a dosage of 150 mg (1 capsule) once a day during 12 months.
干预措施: Vismodegib (Drug)
结局指标
主要结局
The best overall response rate(ORR)
时间窗: 12 months
ORR will be measured by the best overall response (complete response (CR), uncofirmed complete response (CRu) or partial response (PR)) recorded during whole treatment period from the baseline until the end of treatment. ORR will be assessed according to Cheson 1999 for DLBCL and iNHL, according to Abey 2005 (IPCG response criteria) for PCNSL and to Hallek 2008 (IWCLL response criteria) for CLL.
次要结局
- Safety endpoints(Up to 2 year)
- Overall Response rate(12 months)
- Progression Free Survival (PFS)(Up to 3 year)
- Response Duration(Up to 3 year)
- Overall survival(Up to 3 year)
- Correlation between Hedgehog (Hh) signaling in the tumor and the efficacy of Vismodegib(At baseline and at 28 days (+/- 7 days))
研究者
研究点 (10)
Loading locations...
相似试验
已完成
2 期
Vismodegib in Treating Patients With Recurrent or Refractory MedulloblastomaAdult MedulloblastomaNCT00939484National Cancer Institute (NCI)31
已完成
2 期
Vismodegib in Treating Younger Patients With Recurrent or Refractory MedulloblastomaRecurrent Childhood MedulloblastomaNCT01239316National Cancer Institute (NCI)12
已完成
2 期
Study Evaluating the Interest of Vismodegib as Neo-adjuvant Treatment of Basal Cell Carcinoma (BCC)Basal Cell CarcinomaNCT02667574University Hospital, Lille55
终止
2 期
A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic SyndromeMyelodysplastic Syndromes, Myelogenous Leukemia, AcuteNCT01880437Hoffmann-La Roche38
终止
2 期
Erivedge (Vismodegib) in the Treatment of Pediatric Patients With Refractory Pontine GliomaPontine GliomaNCT01774253Giselle Sholler9