A Phase 1/2, Two-Arm, Dose-Finding Study of Natalizumab for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objectives of the study are to evaluate the safety profile and the anti-tumor activity of 2 dose levels of natalizumab in participants with relapsed or refractory multiple myeloma. Secondary objectives are to assess the pharmacokinetic (PK) profile of natalizumab in this study population and to assess peripheral blood mononuclear cell (PBMC) saturation of very late antigen-4 (VLA-4, an α4-integrin) and evaluate possible correlations with clinical activity.
详细描述
Despite no protocol-defined study stopping criteria being met, the sponsor decided to terminate enrollment after the phase 1 portion was complete and to not move into the phase 2 portion of the study. This decision was made due to difficulty enrolling participants and was not due to any safety concerns.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed or refractory multiple myeloma that was treated with or was considered inappropriate for treatment with bortezomib and an IMiD® drug (including an analogue).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
- •Corrected calcium <10.6 mg/dL.
排除标准
- •Candidates for stem cell transplantation willing to undergo transplantation. (Subjects who are candidates for stem cell transplantation, but are not willing to undergo transplant will be eligible for the study.)
- •Autologous stem cell transplantation <3 months post-transplant.
- •Prior allogeneic stem cell transplantation.
- •Nonsecretory myeloma.
- •Plasma cell leukemia (>2000/µL circulating plasma cells by standard cell counting differential), hyperleukocytosis (white blood cells >100,000/µL), clinical evidence of hyperviscosity syndrome, or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), or primary systemic amyloidosis.
- •Subjects who cannot undergo a brain magnetic resonance imaging (MRI) study.
- •Clinically significant (as determined by the Investigator) 12 lead electrocardiogram (ECG) abnormalities, including QTc prolongation (>450 ms in males, >470 ms in females).
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Natalizumab 300 mg
Intravenous (IV) infusions of natalizumab 300 mg once every 28 days for 6 months.
干预措施: BG00002 (natalizumab) (Drug)
Natalizumab 450 mg
Intravenous (IV) infusions of natalizumab 450 mg once every 28 days for 6 months.
干预措施: BG00002 (natalizumab) (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Day 1 up to Day 28
DLTs = any ≥grade 3 toxicity related to treatment; treatment delays of ≥7 days due to any toxicity related to treatment, with the exception of hepatic transaminases; or alanine and/or aspartate aminotransferase (ALT and/or AST) \>3\*upper limit of normal (ULN) with either a total bilirubin \>2\*ULN or an international normalized ratio (INR) \>1.5 related to treatment, or with the appearance of worsening fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia.
Objective Response Rate (ORR)
时间窗: Day 1 up to Month 6
Response rates were classified according to the International Uniform Response Criteria for Multiple Myeloma (Durie et al, 2006).
Number of Participants With Adverse Events (AEs)
时间窗: Day 1 up to Month 6
An AE was defined as any untoward medical occurrence in a participant administered medicinal (investigational) product and that does not necessarily have a causal relationship with this product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. See the adverse events section of the record for more details.
次要结局
- Number Of Participants Who Achieve A Complete Response(Day 1 up to Month 6)
- Kaplan-Meier Estimates for Duration Of Response For Participants With A Response(Day 1 up to Month 6)
- Pharmacokinetic (PK) Profile Of Natalizumab(Cycles 1 and 6: Day 1 (before infusion and 0.25, 2, 6 and 24 hours after infusion), Days 8, 15, 22. Cycles 2-5: Day 1 (before infusion and 0.25 hour after infusion))
- Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)(Cycle 1: Day 1 (1 hour before infusion and 1 and 24 hours after infusion), Days 8, 15, 22. Cycles 2-5: 1 hour before and 1 hour after infusion). Cycle 6: Day 1 (1 hour before infusion and 1 hour after infusion), Days 8, 15, 22.)