A Phase IIb, Multicenter, Open-Label, Safety and Efficacy Study of High Dose Melphalan HCL for Injection (Propylene Glycol-Free)for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 6
- 主要终点
- Mouth Pain Scores according to a Visual Analog Scale
研究概览
简要总结
The purpose of this trial is to confirm the safety and efficacy of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) as a myeloablative conditioning regimen in multiple myeloma patients (MM) undergoing autologous transplantation.
详细描述
The sponsor of the current study is now Acrotech Biopharma, divested from Spectrum Pharmaceuticals Inc. (Spectrum), which licensed the Melphalan HC1 for Injection (Propylene Glycol-Free) product from Ligand Pharmaceuticals , formerly CyDex Pharmaceuticals, Inc. (CyDex). This new injectable form of melphalan HCL incorporates Captisol®, β cyclodextrin sulfobutyl ether sodium salts (also known as [SBE]7m-β-CD), into the product. Captisol is present to facilitate the use of an all aqueous diluent (normal saline) for reconstitution and administration of the freeze-dried product in place of the propylene glycol-ethanol diluent necessary for the currently used melphalan intravenous product. Captisol provides for solubilization and improved stability of the all aqueous reconstituted and diluted infusion solution.
This is the second of two studies supporting product registration. This study will be a multicenter study of high-dose Melphalan HCL for Injection (Propylene Glycol-Free) conducted in 60 patients who have symptomatic MM and qualify for autologous stem cell transplantation (ASCT).
During the Study Period, patients will receive 100mg/m2 of either Melphalan HCL for Injection (Propylene Glycol-Free) on Day -3 and on Day -2 for a total dose of 200mg/m2. Blood samples (5 timepoints post infusion) for population pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula on the first day of administration of melphalan (Day -3) for all patients and then additional blood samples (2 timepoints post infusion) drawn in a subset of patients on the second day of melphalan administration (Day -2).
Following one day of rest after the high dose myeloablative conditioning (Day -1), patients will receive an autologous graft (Day 0).
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
- — 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with symptomatic MM based on IMWG guidelines requiring treatment who are eligible for ASCT.
- •Patients who are 70 years of age or younger at time of transplant. Patients older than 70 years of age may be enrolled on a case-by-case basis if the patient meets local institutional criteria to receive a total melphalan dose of 200 mg/m2 as a conditioning regimen and if approved by the medical monitor.
- •Patients with an adequate autologous graft, defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based on patient body weight.
- •Patients with adequate organ function as measured by:
- •Cardiac function: Left ventricular ejection fraction at rest >40% (documented within 8 weeks prior to Day -3).
- •Hepatic function: Bilirubin <2 × the upper limit of normal and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <3 × upper limit of normal.
- •Renal function: Creatinine clearance >40 mL/minute (measured or calculated/estimated).
- •Pulmonary function: Carbon monoxide diffusing capacity (DLCO)corrected for hemoglobin (Hgb), forced expiratory volume in 1 second (FEV1), forced expiratory vital capacity (FVC), and oxygen saturation >92% on room air (documented within 4 weeks prior to Day -3).
- •Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
排除标准
- •Patients with smoldering MM not requiring therapy.
- •Patients with plasma cell leukemia.
- •Patients with systemic amyloid light chain amyloidosis.
- •Patients with uncontrolled hypertension.
- •Patients with an active bacterial, viral, or fungal infection.
- •Patients with a life expectancy of < 6 months.
- •Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent >5 years previously will be allowed. Cancer treated with curative intent <5 years previously will not be allowed unless approved by the medical monitor.
- •Female patients who are pregnant or breastfeeding.
- •Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 3 months following study treatment with Melphalan HCl for Injection (Propylene Glycol-Free).
- •Patients seropositive for Human Immunodeficiency Virus(HIV).
- •Patients who are unwilling to provide informed consent.
- •Patients receiving other concurrent anticancer therapy (including chemotherapy, radiation, hormonal treatment, or immunotherapy, but excluding corticosteroids) within 30 days prior to the ASCT or planning to receive any of these treatments prior to Day +
- •Patients concurrently participating in any other clinical study involving ASCT.
- •Patients who are hypersensitive or intolerant to any component of the study drug formulation.
研究组 & 干预措施
High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)
Subjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days).
干预措施: High-Dose Melphalan HCL for Injection (Propylene Glycol-Free) (Drug)
High-Dose Melphalan HCL for Injection (Propylene Glycol-Free)
Subjects will receive only High-Dose Melphalan HCL for Injection (Propylene Glycol-free) at 200mg/m2 (100mg/m2/day for two days).
干预措施: Autologous Transplantation (Other)
结局指标
主要结局
Mouth Pain Scores according to a Visual Analog Scale
时间窗: Until Day +30
Baseline VAS for mouth pain and dysphagia will be the VAS score collected prior to receiving the first dose of study medication. Analyses of changes and/or percent changes from baseline in the VAS scores will be analyzed for each time point collected during the 30 day on-treatment period. The minimum and maximum VAS scores during the 30 day on-treatment period will also be calculated for mouth pain and dysphagia, and the time to the minimum and maximum VAS scores will be summarized descriptively.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
时间窗: Up to Day +100
AE coding will be performed using the MedDRA Version 11.0 or greater. The severity of the toxicities will be graded according to the NCI CTCAE Version 4.0 whenever possible. AEs occurring when treatment starts on Day -3 through Day + 100 will be recorded in the AE section of the eCRF and causality will be assigned by the Principal Investigator.
Mucositis Severity according to World Health Organization Scoring System
时间窗: Until Day +30
The baseline measurement will be the last assessment prior to receiving the first dose of study treatment. The on-treatment period will be defined as the day after the first dose of study treatment to 30 days after the last dose of study treatment. The incidence of severe mucositis (WHO Grade 3 or 4) will be summarized by frequencies and percentages. In addition, the incidence of oral mucositis will be summarized by WHO grade. Time from start of the first dose of study medication to peak oral mucositis score will also be calculated.
Treatment Related Mortality
时间窗: Up to Day +100
TRM, which is defined as death not due to disease progression before Day +90/+100, will be calculated. This outcome measure will be summarized by the cumulative incidence estimated with 95% confidence intervals.
次要结局
- Platelet engraftment(Up to Day +100)
- Non-engraftment(Up to Day +100)
- MM response according to International Myeloma Working Group (IMWG) criteria.(At the Day +100 visit)
- Myeloablation(Up to Day +30)
- Neutrophil engraftment(Up to Day +100)