AA Phase IIA Open-Label, Randomized, PK Comparative, Cross-Over Study of Melphalan HCL for Injection (Propylene Glycol-Free) and Alkeran for Injection for Myeloablative Conditioning in MM Patients Undergoing Autologous Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Area Under the Curve (0-t)
研究概览
简要总结
To assess and compare the pharmacokinetics of Melphalan HCL for Injection (Propylene Glycol-Free) versus Alkeran for Injection in multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT).
详细描述
This study will be a multicenter, open-label, randomized, comparative, cross-over study of high-dose Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection conducted in 24 patients who have symptomatic MM and qualify for ASCT.
During the Study Period, patients will be randomized to receive 100mg/m2 of either Melphalan HCl for Injection (Propylene Glycol-Free) or Alkeran for Injection on Day -3 and the alternate drug product on Day -2. Blood samples for pharmacokinetic (PK) evaluation will be withdrawn through an indwelling i.v. cannula each day of melphalan dosing (Day -3 and Day -2).
Following one day of rest after the myeloablative conditioning (Day -1), patients will receive an autologous graft.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with symptomatic MM requiring treatment at diagnosis or anytime thereafter.
- •Patients with MM who qualify for ASCT therapy who have received appropriate primary induction therapy for transplantation.
- •Adult patients (≥ 18 years old) who are 70 years of age or younger at time of transplant; patients greater than 70 years of age may qualify 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 which is defined as an unmanipulated, cryopreserved, peripheral blood stem cell graft containing at least 2 × 106 CD34+ cells/kg based upon patient weight.
- •Patients with adequate organ function as measured by:
- •Cardiac: Left ventricular ejection fraction at rest >40% (documented within 12 weeks prior to Day -3).
- •Hepatic: Bilirubin <2 × the upper limit of normal (ULN) and ALT/AST <3 × ULN.
- •Renal: Creatinine clearance >40 mL/minutes (measured or calculated/estimated).
- •Pulmonary: DLCO, FEV1, FVC >50% of predicted value (corrected for Hgb) or O2 saturation > 92% on room air (documented within 12 weeks prior to Day -3)
排除标准
- •Patients who have never advanced beyond Stage 1 MM since diagnosis.
- •Patients who have previously received more than one autologous stem cell transplant.
- •Patients with plasma cell leukemia.
- •Patients with MM and systemic AL amyloidosis.
- •ECOG performance status ≥
- •Patients with uncontrolled hypertension.
- •Patients with an active bacterial, viral, or fungal infection.
- •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 (positive ß-HCG) or breastfeeding.
- •Female patients of childbearing potential who are unwilling to use adequate contraceptive techniques during and for 1 month following study treatment with Melphalan HCl for Injection (Propylene Glycol-Free).
- •Patients seropositive for 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 21 days prior to the ASCT, or planning to receive any of these treatments prior to study discharge.
- •Patients concurrently participating in any other clinical study.
- •Patients who are hypersensitive or intolerant to any component of the study drug formulation.
研究组 & 干预措施
Melphalan-Alkeran
Subjects begin with treatment Melphalan and crossover to treatment Alkeran
干预措施: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection (Drug)
Melphalan-Alkeran
Subjects begin with treatment Melphalan and crossover to treatment Alkeran
干预措施: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free) (Drug)
Alkeran-Melphalan
Subjects begin with treatment Alkeran and crossover to treatment Melphalan.
干预措施: Melphalan HCL for Injection (Propylene Glycol-Free)/Alkeran for Injection (Drug)
Alkeran-Melphalan
Subjects begin with treatment Alkeran and crossover to treatment Melphalan.
干预措施: Alkeran for Injection/Melphalan HCL for Injection (Propylene Glycol-Free) (Drug)
结局指标
主要结局
Area Under the Curve (0-t)
时间窗: Day -3 and Day -2
AUC (0-t) was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations. The AUC results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
Concentration-Max (Cmax)
时间窗: Day -3 and Day -2
Cmax was one of the pharmacokinetic endpoints to confirm pharmacokinetic similarity between Melphalan HCl for Injection (Propylene Glycol-Free) and Alkeran for Injection in patients with multiple myeloma. Pharmacokinetic similarity was defined as a difference of 20% or less in the 90% confidence intervals (CIs) for the ratios of the pharmacokinetic parameters (calculated using log-transformed data) for the two formulations. The Cmax results provided is the summary of Melphalan PK following Melphalan-Alkeran injection in Sequence 1 and Alkeran-melphalan injection in Sequence 2.
次要结局
- Determination of Myeloablation Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT(30 days)
- Determination of Engraftment Following Melphalan-alkeran Sequence and Alkeran-melphalan Sequence Followed by ASCT(30 days)