An Open Label, Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with Central Nervous System Lymphoma and with Impaired Renal Function Being Treated with High-dose Methotrexate
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Efficacy of Voraxaze
研究概览
简要总结
This phase I-II trial is intented to demonstrate tolerability (i.e. absence of severe non-hematological toxicity) and efficacy of intended intervention with repeated doses of Voraxaze, in addition to leucovorin (LV), in patients with renal impairment or renal failure during previous HD-MTX therapy.
Patients will receive up to 6 cycles of HD-MTX treatment with 14 days between cycles (a maximum delay of 28 days is permitted in order to allow time for a patient to recover from the previous cycle).
详细描述
MTX is used either alone or as part of a combined chemotherapy protocol either in standard or high doses in the treatment of a range of cancers and other diseases.
Dose escalation will be performed using three dose levels of MTX:
Level 1: 3.0 g/m2 Level 2: 3.5 g/m2 Level 3: 4.0 g/m2 Up to 6 patients will be treated at each dose level; each will receive a maximum of 6 cycles of treatment. The dose may be increased in Cycle 3 in individual patients to the next level, if renal function is adequate (GFR ≥ 40 mL/min, or in the case of decreased GFR, the decrease is <10% compared with the pre-treatment value), and absence of grade 3 or 4 non-hematological toxicities.
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
- •Primary or secondary CNSL (PCNSL or SCNSL) confirmed by histology or cytology.
- •Renal insufficiency defined as a glomerular filtration rate (GFR, assessed by CKD-EPI or MDRD equation) of 40-80 mL/min or patients with a GFR >80mL/min who have experienced renal failure, defined as doubling of the serum creatinine compared to the baseline value during a previous HD-MTX treatment.
- •Age ≥ 18 years (male or female).
- •Life expectancy >3 months.
- •Adequate organ function (i.e., bone marrow, liver, lungs) allowing intensive chemotherapy with MTX.
- •Adequate clinical pathology values:
- •Absolute neutrophil count ≥1.0 x 109/L, hemoglobin ≥9mg/dL (transfusion allowed), platelets ≥100 x 109/L.
- •Total bilirubin ≤1.5x the upper limit of normal except for patients with known Gilbert syndrome.
- •Alanine amino-transferase (ALT) and aspartate amino-transferase (AST) ≤2x the upper limit of normal.
- •Alkaline phosphatase ≤2x the upper limit of normal.
- •Prothrombin time within the normal range for the institution.
- •Signed informed consent by the patient or legal representative prior to start of any study specific procedure.
- •Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study in such a manner that the risk of pregnancy is minimized. Acceptable contraceptives include intra-uterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
排除标准
- •Ongoing or expected need for therapy with drugs interfering with MTX-clearance (i.e., beta-lactam antibiotics, NSAIDs, probenicid, salicylates, sulphonamides) or other nephrotoxic drugs.
- •Prior brain radiotherapy within 28 days of first dose of the study drug.
- •Concurrent illness interfering with hydration (i.e., relevant congestive heart failure, SIADH syndrome).
- •Relevant third space (i.e., pleural effusion, ascites, extended edema) precluding HD-MTX treatment.
- •Obesity (body mass index >30 kg/m2).
- •Uncontrolled diabetes.
- •Active hepatitis.
- •HIV-infection.
- •Pregnant or lactating woman.
- •Participation in any other clinical trial either 1 month prior to or during this study.
- •Previous intolerance to any of the drugs used in this study (i.e., MTX, LV)
研究组 & 干预措施
Dose escalation
Patients will receive up to 6 cycles of HD-MTX Treatment Dose escalation will be performed using three dose levels of MTX: 3.0 g/m2, 3.5 g/m2, 4.0 g/m2
干预措施: Voraxaze Injectable Product (Drug)
结局指标
主要结局
Efficacy of Voraxaze
时间窗: 1 year
immediate and sustained reduction in plasma MTX concentration
Tolerability of Voraxaze
时间窗: 1 year
absence of severe non-hematological toxicity
次要结局
- Anti-glucarpidase antibodies(at screening, prior to the MTX infusion at each treatment cycle and on day 28 of the last cycle)
- Dose Limiting Toxicities (DLTs)(1 year)
- MTX toxicities(1 year)
研究者
Stefan Schwartz
PD Dr. med.
Charite University, Berlin, Germany