A Phase I-II Trial of Fenretinide (4-HPR) + Rituximab in Patients With B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Safety, in Terms of Dose-limiting Toxicity (DLT) of 2 Daily Doses of Single Agent Fenretinide (Phase I)
研究概览
简要总结
This phase I/II trial is studying the side effects and best dose of fenretinide and to see how well it works when given together with rituximab in treating patients with B-cell non-Hodgkin lymphoma. Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving fenretinide together with rituximab may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety of fenretinide delivered in a 5 of 7 day regimen. (Phase I) II. To estimate the efficacy (response rates) of fenretinide + rituximab in patients with B-cell non-Hodgkin lymphoma (NHL). (Phase II)
SECONDARY OBJECTIVES:
I. To perform pharmacokinetic studies on patients receiving fenretinide. (Phase I) II. To determine the intratumoral concentrations of fenretinide. (Phase I) III. To evaluate the in vivo mechanism of action of fenretinide. (Phase I) IV. To identify the predictors of response to fenretinide. (Phase I) V. To estimate the response rates, positron emission tomography (PET) response, overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease-free survival (DFS) of patients treated on this study. (Phase I) VI. To estimate the overall survival (OS), progression-free survival (PFS), time to progression (TTP), disease-free survival (DFS), and PET responses of patients treated on this study. (Phase II) VII. To perform pharmacokinetic studies on patients receiving fenretinide. (Phase II) VIII. To determine the intratumoral concentration of fenretinide. (Phase II) IX. To identify the predictors of response to fenretinide and fenretinide + rituximab in B-NHL. (Phase II) X. To evaluate the in vivo mechanism of action of fenretinide in B-NHL. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of fenretinide followed by a phase II study.
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
- •Patients must have a confirmed cluster of differentiation (CD) 20+ lymphoid malignancy
- •All patients with indolent NHL (including Follicular, Marginal Zone, small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL), lymphoplasmacytoid/Waldenström's, nodular lymphocyte predominant Hodgkins) are potentially eligible
- •Patients with Aggressive Lymphoma (including diffuse large B-cell, Burkitt's, Burkitt's-like, B-lymphoblastic) may be considered for this protocol only if unable or unwilling to receive potentially curative intensive therapy
- •All Mantle Cell Lymphoma patients are potentially eligible
- •The World Health Organization (WHO) classification of patient's malignancy must be provided
- •Patients must have a Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) of =< 2
- •Patients should have an expected survival if untreated of at least 60 days
- •Patients must be expected to complete at least 8 weeks of therapy
- •Serum bilirubin less than 2 times the upper limit of normal and no other serious medical condition
- •Creatinine less than 2 times the upper limit of normal and no other serious medical condition
- •Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm or evaluable disease in the bone marrow; patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment; patients with evidence of adenopathy in the neck must have a CT of the neck; (Note: Patients with CLL do not need to have radiographically measurable disease as this is not required to measure response in this disease setting)
- •All patients with an unknown prior bone marrow status or history of bone marrow involvement must have a bone marrow aspirate and biopsy within 28 days of enrollment and no intervening anticancer therapy
- •All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
排除标准
- •Patients known to be human immunodeficiency virus (HIV) positive
- •Patients with evidence of active central nervous system malignancy
- •Pregnant or nursing women
- •Men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- •Concurrent anti-neoplastic therapy
研究组 & 干预措施
Treatment (fenretinide, rituximab)
PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: fenretinide (Drug)
Treatment (fenretinide, rituximab)
PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.
干预措施: rituximab (Drug)
结局指标
主要结局
Safety, in Terms of Dose-limiting Toxicity (DLT) of 2 Daily Doses of Single Agent Fenretinide (Phase I)
时间窗: Number of participants that experienced a dose-limiting toxicity
A group of 3 patients would start treatment ast the dose of 900mg/m\^2 BID, and if none of the 3 experienced a DLT, another 3 would then be treated at that dose. Dose Limiting Toxicity was defined as any related toxicity of grade 4 or 5 on or before the completion of 4 weeks of therapy. Per response evaluation criteria 1999 Cheson Response Criteria for Malignant Lymphoma (CHESON99) for target lesions assessed by either CT or MRI: Complete Response (CR): Complete disappearance of all measurable and non-measurable disease; Complete Response Unconfirmed (CRU): Complete disappearance of all measurable and non-measurable disease, with the exception of all residual nodal masses \>1.5cm in Greatest Transverse Diameter (GTD) reduced by 75% in Sum of the Product of the greatest Diameters (SPD); Partial Response (PR): 50% decrease in the SPD.
Response Rates of B-Non-Hodgkin Lymphoma to the Combination of Rituximab and Fenretinide (Phase II)
时间窗: Up to 7 years
The trial was stratified into rituximab-naïve and rituximab pre-treated patients, and the target response rates for these groups were expected to be 30% and 10%, respectively. The numbers reported below are subjects who achieved a response of partial response or better.
次要结局
未报告次要终点