Phase II Randomized Trial of Population PK Dosed Melphalan With Interleukin-6 Blockade With Siltuximab Vesrus BSA Based Melphalan in Patients With Multiple Myeloma Over Age 60 Undergoing Autologous Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 215
- 试验地点
- 7
- 主要终点
- rate of stringent complete response (sCR)
研究概览
简要总结
The purpose of this study is to see if siltuximab plus population pharmacokinetic (PK)-dosed melphalan works as well as the usual approach (body surface area [BSA]-dosed melphalan) in people with multiple myeloma (MM) who are receiving an autologous stem cell transplant (ASCT) as part of their standard treatment. The researchers will also see if siltuximab in combination with population PK-dosed melphalan works to decrease symptoms after an ASCT, and will study the safety of siltuximab.
For the run-in, 15 patients will receive siltuximab, 11 mg/kg, seven days before and 14 days after autologous hematopoietic stem cell infusion (+/-2 day).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed symptomatic multiple myeloma undergoing autologous HCT with plan off study for melphalan 140 or 200 mg/m2 undergoing HCT within 12 months of diagnosis.
- •At least 60 years of age
- •Have at least 3 million x 10^6 CD34+ cells/kg to be infused
- •KPS performance status >60% or ECOG Performance Status score of 0-2
- •Within 6 weeks prior to enrollment:
- •Diffusion capacity >45% (adjusted for hemoglobin) as predicted by pulmonary function testing.
- •LVEF >45% by MUGA or rest ECHO
- •Clinical laboratory values meeting the following criteria
- •Platelet count ≥ 20 x 10^9/L
- •ALT and AST ≤ 2.5 x ULN o Total bilirubin ≤ 2.5 x ULN; except if the elevation is due to Gilbert's syndrome
- •Calculated creatinine clearance > 40 mL/min
- •Before enrollment, all women are expected to be not of childbearing potential as they will be age 60+.
- •A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug
排除标准
- •Prior exposure to agents targeting IL-6 or the IL-6 receptor
- •Other malignancy within the past 2 years, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix. Prostate cancer under observation may be enrolled after discussion with the MSK Principal Investigator.
- •Concurrent medical condition or disease (eg, autoimmune disease, active systemic Infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in the study
- •Ischemic heart disease requiring intervention in the prior 3 months or uncontrolled heart failure or an uncontrolled arrhythmiaQTc is >460ms by Fridericia. If they have a right or left bundle branch block or intraventricular conduction delay then exclusion will be for >500ms by Friderica.
- •Vaccination with live attenuated vaccines within 4 weeks of first study agent administration
- •Clinically significant infection, including known HIV or hepatitis C infection, or known hepatitis B (Hep B) surface antigen positivity. Patients with Hep B Core positivity can be enrolled if the Hep B PCR is negative, and they are on antiviral suppression. Patients with Hepatitis C Ab positive who are PCR negative and have completed Hepatitis C treatment can be enrolled. HIV with negative viral load on HAART can be enrolled.
- •Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 14 days or 5 half lives before enrollment or is currently enrolled in the treatment stage of an investigational study
- •Had hospitalization for infection or major surgery (eg, requiring general anesthesia) within 2 weeks before enrollment or have not fully recovered from surgery. Note: subjects with surgical procedures conducted under local anesthesia may participate
- •A man who plans to father a child while enrolled in this study or within 3 months after the last dose of study agent.
研究组 & 干预措施
Siltuximab plus population PK-dosed melphalan
For patients randomized to Arm A, the siltuximab, 11 mg/kg, will be administered seven days before and 14 days after autologous hematopoietic stem cell infusion (+/-2 day). Patients will then receive 70mg/m2 of melphalan on Day -2. The melphalan will be infused over 30 minutes. Six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the end of the melphalan infusion for PK testing. The first four time points are +/- 2 min and the last two time points are +/- 5 minutes. The population PK formula in the Insight Rx software will be used to calculate the melphalan dose for Day -1 to achieve a total target area under the curve (AUC) of 13 mg*h/L (+/-1.5). The six PK samples will be collected again after the dose on Day -1 to confirm the total AUC. Patients will receive a minimum of the equivalent of 70mg/m2 and a maximum of the equivalent of 260mg/m2.
干预措施: Siltuximab (Drug)
Siltuximab plus population PK-dosed melphalan
For patients randomized to Arm A, the siltuximab, 11 mg/kg, will be administered seven days before and 14 days after autologous hematopoietic stem cell infusion (+/-2 day). Patients will then receive 70mg/m2 of melphalan on Day -2. The melphalan will be infused over 30 minutes. Six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the end of the melphalan infusion for PK testing. The first four time points are +/- 2 min and the last two time points are +/- 5 minutes. The population PK formula in the Insight Rx software will be used to calculate the melphalan dose for Day -1 to achieve a total target area under the curve (AUC) of 13 mg*h/L (+/-1.5). The six PK samples will be collected again after the dose on Day -1 to confirm the total AUC. Patients will receive a minimum of the equivalent of 70mg/m2 and a maximum of the equivalent of 260mg/m2.
干预措施: Melphalan (Drug)
Standard BSA-dosed melphalan
Patients randomized to Arm B with received Standard of care (SOC) BSA based melphalan dosing at 140 or 200mg/m2 per treating physician on Day -2 and will not receive the siltuximab. The melphalan will be infused over 30 minutes. Six peripheral blood samples of 5 ml in lithium heparin tubes will be collected at 5, 15, 30, 40, 75, and 150 minutes after the end of the melphalan infusion for PK testing. The first four time points are +/- 2 min and the last two time points are +/- 5 minutes.
干预措施: Melphalan (Drug)
结局指标
主要结局
rate of stringent complete response (sCR)
时间窗: 100 days
by modified IMWG based on the day 100 disease evaluation. Urine evaluation will be captured, but response without the urine (unless primary mode of measurement for that patient) will be used for the primary endpoint.
次要结局
未报告次要终点