A Phase I/IIa Multi-Dose Escalation Study to Evaluate Maximum Tolerated Dose (MTD), Pharmacokinetics (PK), Safety and Efficacy of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 5
- 主要终点
- Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT
研究概览
简要总结
This Phase I/IIa clinical study is to test safety and anti-tumor activity of BT062 to define the best dose in treating patients with relapsed or refractory multiple myeloma with multiple doses of BT062.
详细描述
Phase I/IIa, open-label, 3 + 3 multi-dose escalation study. The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD.
The Phase IIa part was to include the MTD/recommended phase II dose (RPTD) expansion cohort in which descriptive statistical methods for evaluation of response, time to event endpoints, and safety were to be performed.
35 subjects in the Safety population, 34 subjects in the ITT and PP populations.
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
- •Diagnosis of active multiple myeloma according to the International Myeloma Working Group diagnostic criteria
- •Relapsed or relapsed/refractory multiple myeloma
- •Previous treatment with both an immunomodulator and a proteosome inhibitor therapy
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status (Zubrod) ≤ 2
- •Ability to understand and willingness to sign a written informed consent document
- •Ability to adhere with the study visit schedule and other protocol procedures
- •Life expectancy of ≥ 12 weeks
- •Normal organ and marrow function
排除标准
- •Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to day 1 or those who have not recovered from AEs due to agents administered more than 3 weeks earlier
- •Treatment with another investigational agent during the study or within 4 weeks before day 1
- •Major surgery within 4 weeks before day 1 (this does not include placement of vascular access device or tumor biopsies)
- •Antineoplastic therapy with biological agents within 2 weeks before day 1
- •Known HAHAs, HACAs, or HAMAs in response to previous MAb therapy
- •Previous treatment with BT062
- •Malignancy within 3 years before day 1, other than the trial indication multiple myeloma and excluding treated non-melanoma skin cancer, superficial bladder cancer and carcinoma in-situ of the cervix
- •Severe diseases of skin, colon, esophagus, or eye within 1 year before day 1, as judged by the Investigator
- •Severe infections necessitating use of antibiotics / antivirals during the screening period
- •Clinically relevant active infection including active hepatitis B or C or human immunodeficiency virus (HBV, HCV, or HIV) or any other concurrent disease which, in the judgment of the investigator, would make the subject inappropriate for enrollment into this study
- •Acute or relevant abnormalities in electrocardiogram (ECG), as judged by the Investigator. These abnormalities can be defined as recent myocardial infarction, uncontrolled cardiac arrhythmias and/or pronounced disturbances of the electrical conduction system of the heart.
- •Significant cardiac disease such as recent myocardial infarction (≤ 6 months prior to day 1), unstable angina, uncontrolled congestive heart failure, uncontrolled hypertension (recurrent or persistent increases in systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg), uncontrolled cardiac arrhythmias, grade 3 (Lown Criteria) or greater cardiac toxicity from prior chemotherapy
- •History of clinically significant drug or alcohol abuse
- •Unwillingness or inability to adhere to the requirements of the study
- •Concomitant therapy with corticosteroids (except as indicated in low dose for other medical conditions such as inhaled steroid for asthma, topical use, or as premedication for administration of certain medications (including BT062) or blood products and for treatment of infusion reactions if needed)
- •Concomitant antineoplastic therapies including chemotherapy, radiotherapy, or biological agents during the study
- •Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he or she are included in the study
- •Breast-feeding
- •Unwillingness to use an effective contraceptive method during the study and at least 3 months after administration of study drug - unless subject is naturally infertile. (Acceptable contraceptive methods include oral or injectable contraceptives, intrauterine devices (IUD), double-barrier method, contraceptive patch, surgical sterilization, or condoms).
- •Positive serum or urine pregnancy test
研究组 & 干预措施
BT062
BT062 was to be administered as single-dose IV infusions via a 0.22 μm in-line filter preferably in a forearm vein, according to medically accepted procedures on Days 1, 8, and 15 of each 28-day cycle. Alternatively BT062 may have been administered through a central venous line or a peripherally inserted central catheter (PICC). Other administration routes were only to be allowed after approval from Biotest. Each subject was to be monitored carefully for the effects of exposure to BT062. No subject was to have received more than 3 doses of BT062 per 28-day treatment cycle.
干预措施: BT062 (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT) - Number of Participants With at Least 1 DLT
时间窗: Starting with first study drug administration until 30-day follow-up visit (average 4.99 months)
The primary safety variable was to determine the incidence of DLTs in subjects with relapsed or relapsed/refractory multiple myeloma treated with BT062.
Maximum Tolerated Dose (MTD)
时间窗: First 28-day cycle
The Phase I part of the study was to include the dose escalation cohort; a conventional dose escalation design, following 3 + 3 rules was chosen to define the MTD. Only DLTs occurring in cycle 1 for each subject were counted in the dose escalation decisions. Three subjects were treated at the first or newest dose level as available. If none of the 3 subjects experienced a DLT during Cycle 1, three subjects could be treated at the next dose level as available. In case of a DLT the cohort was expanded to up to 6 subjects. If not more than 1 of these 6 subjects experienced a DLT during Cycle 1, a first subject could be treated at the next dose level. If 2 or more of the 6 subjects experienced a DLT during Cycle 1 the dose escalation was stopped. The highest dose level at which \< 2 of 6 subjects experienced a DLT is defined as the MTD.
次要结局
- Qualitative and Quantitative Toxicities of BT062(Starting with first study drug administration until 30-day follow-up visit (average 4.99 months))
- Time to Progression (TTP), Progression Free Survival (PFS) and Overall Survival (OS)(Starting with first study drug administration until death or 3 years from first study treatment.)
- Multi-dose Pharmacokinetics Properties of BT062 - Cmax(Starting with first study drug administration until 30-day follow-up visit (average 4.99 months).)
- Anti-tumor Activity of BT062 in Subjects With Relapsed or Relapsed/Refractory Multiple Myeloma by Number of Participants With Objective Response(ORR) and/or Clinial Benefit(CBR) Based on the International Myeloma Working Group Uniform Response Criteria(On day 1 of each treatment cycle (on a monthly basis) starting with first study drug administration until Close Out visit (average 3.84 months).)