NCT03013933已完成1 期
A Phase I Trial of Brentuximab Vedotin Plus MDR1 Inhibitors in Relapsed/Refractory Hodgkin Lymphoma
City of Hope Medical Center1 个研究点 分布在 1 个国家目标入组 29 人开始时间: 2017年5月3日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity
研究概览
简要总结
This phase I trial studies the side effects and best dose of brentuximab vedotin and cyclosporine when given together with verapamil hydrochloride in treating patients with Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Immunosuppressive therapies, such as cyclosporine, may improve bone marrow function and increase blood cell counts. Verapamil hydrochloride may increase the effectiveness of brentuximab vedotin by overcoming drug resistance of the cancer cells. Giving brentuximab vedotin, cyclosporine, and verapamil hydrochloride may work better in treating patients with Hodgkin lymphoma.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate the safety and tolerability of the combination of brentuximab vedotin (BV) plus MDR1 inhibitors cyclosporine (CsA)/verapamil hydrochloride (verapamil [VRP]).
SECONDARY OBJECTIVES:
I. Obtain estimates of overall response rate (ORR), complete response (CR) rate, and response duration in patients treated with the combination of BV plus CsA/VRP.
II. Estimate overall and progression-free survival in patients treated with the combination of BV plus CsA/VRP.
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent
- •Voluntary written informed consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- •Weight over 40 kg
- •Life expectancy of greater than 3 months
- •Patients must have histologically documented or cytologically confirmed Hodgkin lymphoma
- •Patient must have measurable disease > 1.5 cm evidenced by computed tomography (CT) of the neck/chest/abdomen (abd)/pelvis or CT/positron emission tomography (PET) scans
- •Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or from archival tissue of a biopsy that was performed after the most recent systemic therapy. Exception can be granted by the principal investigator (PI) if a biopsy is not feasible and/or safe
- •Patients must be either refractory to or relapsed after at least 1 line of therapy
- •Prior brentuximab vedotin is allowed; expansion cohort is defined as:
- •Expansion cohort: BV refractory: Patient who had prior exposure to BV, and either - achieved a best response of stable disease (SD) or progressive disease (PD) or - achieved a best response of complete response (CR)/PR but developed PD while on active BV treatment
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
- •Prior chemotherapy or radiation therapy is allowed if received >= 3 weeks before study enrollment
- •Prior hematopoietic transplantation is allowed (autologous and/or allogeneic)
- •Absolute neutrophil count (ANC) >= 1,000/mm^3; filgrastim can be given prior to enrollment to achieve target ANC >= 1000/uL (to be performed within 10 business days prior to day 1)
- •Platelets >= 50,000/mm^3; NOTE: platelet transfusion and packet red blood cell transfusion can be given prior to enrollment to achieve a target platelet (Plt) >= 50,000/uL and hemoglobin of >= 8.5 g/dL (to be performed within 10 business days prior to day 1)
- •Hemoglobin >= 8.5 g/dL (to be performed within 10 business days prior to day 1)
- •Total bilirubin within 1.5 x the upper limit of normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible (to be performed within 10 business days prior to day 1)
- •Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) unless demonstrated Hodgkin lymphoma involvement of the liver (to be performed within 10 business days prior to day 1)
- •Alanine aminotransferase (ALT) =< 3 x ULN unless demonstrated Hodgkin lymphoma involvement of the liver (to be performed within 10 business days prior to day 1)
- •Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula and/or 24 hour (hr) urine analysis as needed (to be performed within 10 business days prior to day 1)
- •If not receiving anticoagulants: international normalization ratio (INR) OR prothrombin (PT) =< 1.5 x ULN; if on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 10 business days prior to day 1)
- •If not receiving anticoagulants: activated partial thromboplastin time (aPTT) =< 1.5 x ULN; if on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 10 business days prior to day 1)
- •Female of childbearing potential: negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 10 business days prior to day 1)
- •In patients who are to receive VRP, base systolic blood pressure (SBP) > 110; diastolic blood pressure (DBP) > 60 and baseline heart rate > 60 (to be performed within 10 business days prior to day 1)
- •Cardiac function (12 lead-electrocardiogram [ECG] versus [vs] non 12 led ECG) shows no underlying arrhythmia or heart blocks (for VRP only) (to be performed within 10 business days prior to day 1)
- •Female subjects must be either post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intra-uterine deice, diaphragm with spermicide, condom with spermicide, or abstinence) beginning prior to study entry, for the duration of the study, and for six months duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Male subjects must agree to use an acceptable method of contraception beginning prior to study entry, for the duration of the study, and for six months following duration of study participation
排除标准
- •Patients who are hematopoietic stem cell transplant candidates are excluded
- •Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
- •Patients may be on steroids prior to initiation of treatment, provided that, by cycle 1 day 1, steroid use is tapered down to less than or equal to 20 mg/day of prednisone
- •Patients may not be receiving any other investigational agents, or concurrent biological therapy, chemotherapy, or radiation therapy
- •Active graft versus host disease (GVHD) or on immunosuppressive medication of GVHD
- •Recent infection requiring intravenous anti-infective treatment that was completed =< 14 days before enrollment
- •Unresolved toxicities from prior anticancer therapy, defined as having resolved to Common Terminology Criteria for Adverse Events (CTCAE, version 4.03), grade 0 or 1, with the exception of alopecia
- •Baseline grade II peripheral neuropathy
- •Hypersensitivity to BV or history of allergic reaction attributed to compounds of similar chemical or biologic composition of BV
- •Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
- •Patients should not have any uncontrolled illness including ongoing or active infection
- •Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
- •Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
- •Significant screening electrocardiogram (ECG) abnormalities including, but not limited to, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) >= 470 msec; subjects with a cardiac pacemaker who have a QTc interval of >= 470 msec may be eligible if these findings are considered not clinically significant as documented via a cardiology evaluation
- •Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
- •Patients with active central nervous system (CNS) disease or history of brain metastases are excluded from study
- •Known active human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; subjects who have an undetectable HIV viral load with CD4 >= 200 and are on highly active antiretroviral therapy (HAART) medication are allowed; subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded; patients who have had hepatitis C but have finished treatment and are PCR negative will be allowed; (testing to be done only in patients suspected of having infections or exposures)
- •Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued
- •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
- •Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)
研究组 & 干预措施
Treatment (cyclosporine, verapamil, brentuximab vedotin)
Experimental
Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Brentuximab Vedotin (Drug)
Treatment (cyclosporine, verapamil, brentuximab vedotin)
Experimental
Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclosporine (Drug)
Treatment (cyclosporine, verapamil, brentuximab vedotin)
Experimental
Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacokinetic Study (Other)
Treatment (cyclosporine, verapamil, brentuximab vedotin)
Experimental
Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Verapamil (Drug)
Treatment (cyclosporine, verapamil, brentuximab vedotin)
Experimental
Patients receive cyclosporine PO BID on days 1-5, verapamil hydrochloride PO QID on days 1-5, and brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Verapamil Hydrochloride (Drug)
结局指标
主要结局
Dose-limiting toxicity
时间窗: Up to 21 days
Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
次要结局
- Complete response rate assessed by Cheson 2014 criteria(Up to 2 years)
- Duration of complete response(Up to 2 years)
- Overall response rate (complete response + partial response)(Up to 2 years)
- Duration of overall response(Up to 2 years)
- Overall survival(From start of protocol treatment to time of death (due to any cause), assessed up to 2 years)
- Incidence of adverse events assessed(Up to 2 years)
- Progression-free survival(From start of treatment to time of disease progression or death due to any cause, whichever occurs first, assessed up to 2 years)
研究者
研究点 (1)
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