A Phase I/II Study of Veltuzumab (IMMU-106, hA20), a Humanized Anti-CD20 Monoclonal Antibody, Combined With Milatuzumab (IMMU-115, hLL1), a Humanized Anti-CD74 Monoclonal Antibody, in Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Dose Limiting Toxicity (DLT) for Phase I Patients
研究概览
简要总结
A phase I dose escalation study of veltuzumab and milatuzumab in relapsed and refractory B-cell NHL. The phase I study will be followed by a pilot phase II study.
详细描述
A phase I/II study of veltuzumab combined with milatuzumab in relapsed and refractory non-Hodgkin's lymphoma. Both agents are well-tolerated in early phase clinical testing with infusion reactions as the primary observed toxicity. Preclinical testing in vitro and in vivo have demonstrated single agent activity for both veltuzumab and milatuzumab. In mantle cell lymphoma cell lines and SCID mouse models, synergist effects were observed when milatuzumab was combined with rituximab. Veltuzumab has several advantages over rituximab including slower off-rates, shorter infusion times, higher potency, and improved therapeutic responses in animal models. Previous and ongoing clinical investigations support the concept of combining monoclonal antibodies in NHL.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed B-cell non-Hodgkin lymphoma (NHL), including any of the following:
- •Marginal zone lymphoma
- •Waldenstrom macroglobulinemia (lymphoplasmacytic lymphoma)
- •Follicular lymphoma
- •Mantle cell lymphoma
- •Relapsed or refractory disease after ≥ 1 prior therapy
- •Patients with rituximab-refractory disease (defined as having less than a partial response to the prior rituximab-containing regimen) or rituximab-sensitive disease (defined as having a complete response or partial response to the last rituximab-containing regimen [provided it has been ≥ 3 months since the last dose of rituximab]) are eligible.
- •Age >18 years.
- •Eastern Cooperative Oncology Group (ECOG)performance status 0-
- •Patients must have normal organ and marrow function as defined below:
- •Absolute neutrophil count ≥ 1000/μL
- •Platelets ≥ 75,000/μL
- •Total bilirubin ≤ 2.0 X institutional upper limit of normal
- •AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
- •Creatinine ≤ 2.0 mg/dL
- •Patients who have relapsed after stem cell transplant are eligible for this trial.
- •Patients with active Hepatitis B infection are not eligible.
- •Non-pregnant and non-nursing. Women of child bearing potential and men must agree to use contraception prior to study entry and for duration of study participation.
- •Must possess the ability to understand and the willingness to sign a written informed consent document.
- •Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension >10 mm or in the case of Waldenstrom's macroglobulinemia, the presence of an IgM paraprotein level 2x the upper limit of normal.
排除标准
- •Must be recovered from all toxicities from prior therapy or radiation (excluding alopecia).
- •No known CNS lymphoma.
- •History of documented human anti-globulin antibodies.
- •No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations.
- •HIV-positive patients.
- •Pregnant women.
- •Patients with secondary malignancies with exception of non-melanomatous skin cancers.
结局指标
主要结局
Dose Limiting Toxicity (DLT) for Phase I Patients
时间窗: up to 2 years
Dose-limiting toxicity was assessed during induction therapy for phase I.
Maximum Tolerated Dose (MTD)for Phase I Patients
时间窗: up to 2 years
Patients received a fixed dose of Veltuzumab IV 200 mg/m2 and Milatuzumab was dose escalated
Overall Objective Response Rate
时间窗: Up to 2 years
Per International Response Criteria (Cheson JCO 2007) for target lesions and assessed by CT, MRI or PET: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses; Overall Response (OR) = CR + PR.
次要结局
- Progression-free Survival (PFS)(up to 2 years)
- Fcγ-receptor Polymorphism Response to Treatment(up to 2 years)
- Quantitative T-, B-, and NK-cell Subsets Using Flow Cytometry(up to 1 year)
- Access Pharmacokinetics Through Cmax(0, 24, 48, 72, 96 and 120 hours post-dose)
- Monitor Human Anti-veltuzumab Antibodies and Human Anti-milatuzumab (HAHA)(up to 36 weeks)
- Access Pharmacokinetics Through AUC0-∞ (Area Under Curve)(0, 24, 48, 72, 96 and 120 hours post-does)
研究者
Beth Christian
Principal Investigator
Ohio State University Comprehensive Cancer Center