Phase 1/2 Study of VELCADE (Bortezomib), Nipent (Pentostatin), and Rituxan (Rituximab) (VNR) in Subjects With Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- CR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
研究概览
简要总结
This is a phase 1/2 Study of VELCADE (bortezomib), Nipent (pentostatin), and Rituxan (rituximab) (VNR) in Subjects with Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma.
详细描述
Number of Subjects: During the Phase 1 part of the study as many as 15 subjects may be enrolled, based on the dose escalation scheme; the actual number of subjects enrolled will depend on the dose level at which the maximum tolerated dose (MTD) is established.
During the Phase 2 part of the study, approximately 15 subjects will be enrolled in order to obtain a total 30 response-evaluable subjects.
Study Objectives:
The primary objectives of this study are:
• Assess the CR and ORR following treatment with VELCADE (bortezomib), Nipent (pentostatin) and Rituxan (rituximab) (VNR) in subjects with follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) who have relapsed or been refractory after receiving at least 1 prior therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary written informed consent.
- •Male or female subject 18 years of age and older
- •Karnofsky Performance Status (KPS) score of 50%. ECOG Performance Status score greater than
- •Histologically confirmed follicular Grade 1-3a, marginal zone or mantle cell NHL.
- •Relapsed or progressive disease after at least 1 prior chemotherapy requiring treatment.
- •Bi-dimensionally measurable disease with at least 1 lesion 2 cm in a single dimension
- •Hematologic, hepatic, and renal function parameters.
- •Recovered fully from any significant toxicity associated with prior surgery, radiation treatments, chemotherapy, biological therapy, autologous bone marrow or stem cell transplant, or investigational drugs
- •Expected survival of 3 months
- •Accepted birth control methods during treatment and for 12 months after completion of treatment.
排除标准
- •Follicular lymphoma Grade 3b
- •History of allergy to any of the study medications, their analogues, murine proteins, or excipients in the various formulations
- •Grade 2 peripheral neuropathy or clinical examination within 14 days before enrollment
- •Serum creatinine 2.5 mg/dL within 14 days before enrollment.
- •Absolute neutrophil count (ANC) < 1,000/L, platelet count < 70,000/L within 14 days before enrollment
- •Aspartate transaminase (AST [SGOT]) and alanine transaminase (ALT/SGPT]) > 2 x the upper limit of normal (ULN), total bilirubin > 3 ULN
- •Rituxan refractory or refractory to anti-CD20 radioimmunotherapy (no response to prior Rituxan or prior Rituxan-containing regimen, or a response with a TTP of less than 6 months)
- •Cancer radiotherapy, biological therapy, or chemotherapy within 3 weeks prior to Study Day 1 (6 weeks if nitrosurea or mytomycin-C)
- •Prior lymphoma vaccine therapy within 12 months to Study Day 1
- •Prior antibody therapy for lymphoma (including radioimmunotherapy) within 6 months prior to Study Day 1
- •Autologous bone marrow or stem cell transplant within 6 months prior to Study Day 1
- •Known history of hepatitis or hepatic disease.
- •Presence of central nervous system (CNS) lymphoma
- •Known history of HIV infection or AIDS
- •Histologic transformation (Follicular or Marginal zone to diffuse large B cell lymphoma [DLBCL]
- •Presence of pleural or peritoneal effusion with positive cytology for lymphoma
- •Another primary malignancy requiring active treatment
- •Serious non-malignant disease (e.g., congestive heart failure [CHF], hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions (including psychiatric), which would compromise protocol objectives n the opinion of the Investigator and/or Sponsor
- •New York Heart Association Class III or IV (Appendix D) cardiac disease
- •Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1
- •Female subject who is pregnant or currently breast-feeding
- •Received other investigational drugs with 14 days before enrollment
- •Hypersensitivity to bortezomib, pentostatin, rituximab, boron or mannitol.
研究组 & 干预措施
Part 1: establish MTD
Part 1 consists of dosing to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT).
干预措施: MTD of Velcade, Nipent and Rituxan established in Part 1 (Drug)
Part 2: The MTD from Part 1
During the Phase 2 part of the study, approximately 24 additional subjects will be enrolled in order to obtain a total of 30 response-evaluable subjects treated at the maximum tolerated dose.
干预措施: MTD of Velcade, Nipent and Rituxan established in Part 1 (Drug)
结局指标
主要结局
CR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
时间窗: up to 48 months
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
ORR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
时间窗: up to 48 months
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
次要结局
- Maximum Tolerated Dose(Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48)
- Rate of progression of disease(Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48)
研究者
Glenn Mills
Professor of Medicine
Louisiana State University Health Sciences Center Shreveport