An Open-label Phase I, Dose Escalation Study of the Safety and Tolerability of OPD5 as Myeloablative Conditioning Regimen Followed by Autologous Stem Cell Transplant (ASCT) for Patients With Relapsed Refractory Multiple Myeloma (RRMM)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- Incidence of clinically significant changes in clinical laboratory parameters
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of a single infusion of OPD5 before Autologous Stem Cell Transplant in patients with RRMM. The study will evaluate increasing doses of OPD5 to find the best dose and to assess any side effects. Each patient will be assigned to a dose cohort of 3-6 patients to receive one single dose of OPD5. Each patient will be hospitalized for about 14 days from the OPD5 infusion and then have monthly visits to the clinic for 3 months and then every third month until disease progression or starting new myeloma treatment, maximum up to 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Male or female, between the ages of 18 years and 70 years at the planned time of study treatment; patients greater than 70 years of age may qualify on a case by case basis
- •Diagnosis of multiple myeloma
- •Received a previous Autologous Stem Cell Transplantation ( ASCT) (single or tandem) that resulted in disease progression within 24 months
- •Received at least 2 prior lines of therapy
- •Refractory to previous treatment with a Proteasome Inhibitor (PI), an immunomodulatory drug (IMiD) and an anti-Cluster of Differentiation 38 monoclonal antibody (anti-CD38 mAb)
- •Male and women of childbearing potential agrees to use contraception during the treatment period and during a specified time period after the last dose
排除标准
- •Prior treatment with melphalan flufenamide (melflufen) or OPD5
- •Any medical condition that may interfere with safety or participation in this study
- •Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
- •Prior allogeneic stem cell transplantation or prior salvage ASCT
研究组 & 干预措施
Dose cohort 1
In dose cohort 1, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level of 30 mg/m2 (dose based on body surface area)
干预措施: OPD5 (Drug)
Dose cohort 2
In dose cohort 2, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 1
干预措施: OPD5 (Drug)
Dose cohort 3
In dose cohort 3, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 2
干预措施: OPD5 (Drug)
Dose cohort 4
In dose cohort 4, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 3
干预措施: OPD5 (Drug)
Dose cohort 5
In dose cohort 5, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 4
干预措施: OPD5 (Drug)
Dose cohort 6
In dose cohort 6, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 5
干预措施: OPD5 (Drug)
Dose cohort 7
In dose cohort 7, treatment with OPD5 solution will be given as one single i.v. infusion over 30 minutes at a dose level decided based on the results from Dose Cohort 6
干预措施: OPD5 (Drug)
结局指标
主要结局
Incidence of clinically significant changes in clinical laboratory parameters
时间窗: 30 days post OPD5 treatment with ASCT
Incidence of clinically significant adverse findings in vital signs
时间窗: 30 days post OPD5 treatment with ASCT
Incidence of clinically significant adverse findings in electrocardiograms (ECGs)
时间窗: 30 days post OPD5 treatment with ASCT
Severity of clinically significant adverse findings in electrocardiograms (ECGs)
时间窗: 30 days post OPD5 treatment with ASCT
Severity of clinically significant adverse findings in vital signs
时间窗: 30 days post OPD5 treatment with ASCT
Incidence and grade of Treatment Emergent Adverse Events (TEAEs)
时间窗: 30 days post OPD5 treatment with ASCT
Including frequency and grade of defined Dose Limiting Toxicities
Magnitude of clinically significant changes in clinical laboratory parameters
时间窗: 30 days post OPD5 treatment with ASCT
The number of deaths not related to relapse or progression
时间窗: 100 days post OPD5 treatment with ASCT
Incidence of clinically significant adverse findings in other physical examination parameters
时间窗: 30 days post OPD5 treatment with ASCT
Severity of clinically significant adverse findings in other physical examination parameters
时间窗: 30 days post OPD5 treatment with ASCT
Incidence of mucositis
时间窗: 30 days post OPD5 treatment with ASCT
Severity of mucositis
时间窗: 30 days post OPD5 treatment with ASCT
Using World Health Organization (WHO) oral toxicity scale, from 0 (no change) to 4 (oral feeding is not possible)
次要结局
- Best Response(30 days post OPD5 treatment with ASCT)
- Pharmacokinetics Area under the curve AUC(0-t) for OPD5 and the metabolites desethyl-melflufen and melphalan(Day -1 (the day of OPD5 infusion))
- Overall Response Rate (ORR)(approximately 100 days post OPD5 treatment with ASCT)
- Duration of response (DOR)(approximately 12 months)
- Time to progression (TTP)(approximately 12 months)
- Time to next treatment (TTNT)(approximately 12 months)
- Progression Free Survival (PFS)(approximately 12 months)
- Pharmacokinetics AUC(0-infinity) for OPD5 and the metabolites desethyl-melflufen and melphalan(Day -1 (the day of OPD5 infusion))
- Pharmacokinetics elimination half-life (t½) for OPD5 and the metabolites desethyl-melflufen and melphalan(Day -1 (the day of OPD5 infusion))
- Pharmacokinetics Cmax for OPD5 and the metabolites desethyl-melflufen and melphalan(Day -1 (the day of OPD5 infusion))
- Time to hematological recovery(approximately Day 14)
- Time to myeloablation(approximately Day 14)
- Minimal Residual Disease (MRD) status by Next Generation sequencing (NGS) in patients that achieve a CR or VGPR.(approximately Day 100)