Phase Ia/Ib Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Ch mAb 11-1F4
研究概览
简要总结
The purpose of this study is to examine the tolerance, safety, pharmacokinetics, and possible clinical benefit of the good manufacturing practice (GMP)-grade amyloid fibril-reactive chimeric (Ch) IgG1 mAb 11-1F4 in patients with amyloid light-chain (AL) amyloidosis.
The phase 1a part will involve at least 3 patients and a maximum of 18 patients. The first patient will receive the starting dose of the antibody and, if tolerated, the following patients will each receive (if tolerated) progressively higher doses of the antibody. Patients in part 1a of the trial will receive only one infusion of the drug. Patients treated in the phase 1a part receive lower dosage which might not be effective.
Once the maximal tolerated dosage is established during the phase 1a part, the investigators will accrue patients to the phase 1b part of the trial. Patients will receive 4 infusions, once each week for 4 weeks. Patients who were treated in the part 1a of the trial and showed no toxicity can be also treated in the part 1b of the trial. The first patient will receive the starting dose of the antibody and, if tolerated, the following patients will each receive (if tolerated) progressively higher doses of the antibody. When the investigators reach the maximum tolerated dose without toxicity, the investigators will enroll another 4 patients to receive the same dose. If there are no toxicities, another 4 patients will be treated at the next dose level, and so forth. Patients treated in Phase 1b may receive lower dosages which might not be effective. The goal of Phase 1b is to establish the tolerance and possible beneficial effects of 11-1F4. If successful, treatment with this antibody would represent a novel approach in the care of individuals with AL amyloidosis.
详细描述
Presently, treatment of patients with amyloid light chain (AL) amyloidosis is limited to reducing production of the amyloid-forming light-chain protein by giving conventional or high-dose (with stem cell transplant) anti-plasma cell chemotherapy, as used for patients with multiple myeloma. Although this approach has extended survival, the prognosis remains poor due to the persistence or progression of the amyloid deposits in vital organs, such as the heart or kidney. A different treatment strategy would be to attempt to reduce and/or eliminate these deposits. This study evaluates this by administering an anti-amyloid monoclonal antibody, 11-1F4. This compound has been shown to reduce/destroy this material in an experimental animal model of amyloidosis.
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
- 21 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 diagnosis of AL amyloidosis based on accepted clinical and laboratory criteria.
- •Patients are greater than 21 years old.
- •Female patients are not of child bearing potential or if they are of child bearing potential, they must not be pregnant or breast-feeding.
- •Patients have a life expectancy greater than 3 months.
- •Patients have an Eastern Cooperative Oncology Group (ECOG)-specified performance status of less than or equal to
- •Patients to be included are those with measurable, localized amyloid deposits (larynx, subcutaneous tissue, muscle, lung, lymph nodes) or clinically evident systemic disease (liver, kidney, heart, etc).
- •Only patients with prior systemic therapy with relapsed/refractory disease are eligible, unless they have declined or are not eligible for high-dose melphalan and autologous hematopoietic stem cell transplant (HSCT) or any other standard therapy that has been known to be life-prolonging or life-saving.
- •Patients have adequate organ function.
- •Patients with cancer are eligible provided they meet specific criteria.
- •Patients must provide signed, written, informed consent and be willing and able to comply with eligibility requirements, scheduled, visits, and follow-up studies.
排除标准
- •Non-AL amyloidosis.
- •Renal failure (on dialysis).
- •Females who are pregnant or breast-feeding.
- •ECOG Performance Status greater than
- •Seriously limited cardiac, renal, or hepatic function.
- •Uncontrolled infection or significant co-morbidity (e.g., uncontrolled diabetes, severe diarrhea).
研究组 & 干预措施
Phase Ia
Administration of Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4:
A 1-patient cohort will be infused with 0.5 mg/m2 of Ch 11-1F4 and, if tolerated, the doses in the next patients will be increased to 5, 10, 50, 100, 250, and finally, 500 mg/m2. All individuals will be evaluated prior to treatment, after infusion weekly for four weeks, as well as at 8 weeks.
干预措施: Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4 (Drug)
Phase Ib
Administration of Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4:
Subjects will receive four weekly infusions of the monoclonal anti-body at Dose Level 1 (0.5 mg/m2). If tolerated, the doses in the next patients will be increased to 5, 10, 50, 100, 250, and finally, 500 mg/m2. When the highest tolerated dose is reached without toxicity in 2 patients, an additional 4 patients will be enrolled and infused at that dose. Escalation or de-escalation will continue until we have determined the highest dose level at which less than 2 patients experience toxicity. All individuals will be evaluated prior to each course of treatment, as well as at weeks 5, 8, and 12.
干预措施: Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Ch mAb 11-1F4
时间窗: 2 years approximately
The MTD of a single application of Ch mAb 11-1F4 is defined as the highest safely-tolerated dose (mg/m2) where 0 patients experiences Dose Limiting Toxicity.
次要结局
- Number of subjects with positive amyloid-related organ response(12 weeks)
- Estimated mean area under the curve (AUC) for Ch mAb 11-1F4(Phase 1a: 1, 2, 24 hours post start of infusion; then post-infusion week 1, 2, 3, 4, 8. Phase 1b: pretreatment, 1, 2, 24 hours post start of infusion; then post-infusion week 5, 8, 12.)
- Number of participants with adverse events(2 years approximately)