Prospective Phase I/II Trial to Jointly Optimize the Administration Schedule(s) and Dose(s) of Melphalan for Injection (Evomela) as a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Optimal Dose and Schedule of Evomela Prior to Autologous Transplant.
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of melphalan hydrochloride in treating participants with newly-diagnosed multiple myeloma who are undergoing a donor stem cell transplantation. Giving chemotherapy before a donor stem cell transplantation helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant, they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving melphalan hydrochloride before a donor stem cell transplantation may work better than standard chemotherapy in helping to prevent multiple myeloma from coming back.
详细描述
PRIMARY OBJECTIVES:
I. To determine the optimal dose and schedule of melphalan for injection (melphalan hydrochloride [Evomela]) prior to autologous hematopoietic stem cell transplantation (auto-HCT) for multiple myeloma (MM).
II. To collect the pharmacokinetic data and compare the exposure-response evaluations between the 2 infusion schedules.
SECONDARY OBJECTIVES:
I. To determine the incidence of treatment related mortality (TRM) at day 90 after auto-HCT in newly diagnosed myeloma patients treated on different schedules and doses of Evomela.
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
- 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 non-relapsed multiple myeloma in complete response (CR), partial remission (PR), very good partial remission (VGPR), or symptomatic stable disease (no evidence of progression) including patients with light chain multiple myeloma (MM) detected in the serum by free light chain assay OR
- •Patients with non-secretory multiple myeloma (absence of a monoclonal protein [M protein] in serum as measured by electrophoresis [serum protein electrophoresis (SPEP)] and immunofixation (serum immunofixation electrophoresis [SIFE]) and the absence of Bence Jones protein in the urine [urine protein electrophoresis (UPEP)] defined by use of conventional electrophoresis and immunofixation [urine immunofixation electrophoresis (UIFE) techniques]) but with measurable disease on imaging studies like magnetic resonance imaging (MRI), computed tomography (CT) scan or positron emission tomography (PET) scan.
- •Patients who have received at least two cycles of initial systemic therapy and are within 2 to 12 months of the first dose. Mobilization therapy is not considered initial therapy.
- •Karnofsky performance score 70% or higher.
- •Left ventricular ejection fraction at rest > 40% within 3 months of registration.
- •Bilirubin < 2 x the upper limit of normal (except patients with Gilbert syndrome in whom bilirubin level of > 2 x upper normal limit will be allowed)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x the upper limit of normal.
- •Creatinine clearance of >= 40 mL/min, estimated or calculated using the Cockcroft-Gault equation.
- •Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), forced vital capacity (FVC) > 50% of predicted value (corrected for hemoglobin) within 3 months of registration.
- •All female and male subjects of reproductive potential must consent to the use of effective contraceptive methods as advised by the study doctor during treatment.
- •Signed informed consent form.
排除标准
- •Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
- •Patients seropositive for the human immunodeficiency virus (HIV).
- •Patients with history of myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- •Patients participating in an investigational new drug protocol within 14 days before enrollment.
- •Female patients who are pregnant (positive beta-human chorionic gonadotropin [b-HCG]) or breast feeding.
- •Prior hematopoietic cell transplantation allogeneic or autologous (A prior autologous HCT will be allowed as long as it was part of tandem transplantation).
- •Prior organ transplant requiring immunosuppressive therapy
研究组 & 干预措施
Group 1 (melphalan hydrochloride, HSCT, filgrastim)
PREPARATIVE REGIMEN: Participants receive melphalan hydrochloride IV over 30-60 minutes on day -2.
TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes.
POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz SC QD starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an ANC of 0.5 x 10^9/L.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Group 1 (melphalan hydrochloride, HSCT, filgrastim)
PREPARATIVE REGIMEN: Participants receive melphalan hydrochloride IV over 30-60 minutes on day -2.
TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes.
POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz SC QD starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an ANC of 0.5 x 10^9/L.
干预措施: Filgrastim-sndz (Biological)
Group 1 (melphalan hydrochloride, HSCT, filgrastim)
PREPARATIVE REGIMEN: Participants receive melphalan hydrochloride IV over 30-60 minutes on day -2.
TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes.
POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz SC QD starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an ANC of 0.5 x 10^9/L.
干预措施: Melphalan Hydrochloride (Drug)
Group 2 (melphalan hydrochloride, HSCT, filgrastim)
PREPARATIVE REGIMEN: Participants receive melphalan hydrochloride IV over 8-9 hours on day -2.
TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes.
POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz SC QD starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an ANC of 0.5 x 10^9/L.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Group 2 (melphalan hydrochloride, HSCT, filgrastim)
PREPARATIVE REGIMEN: Participants receive melphalan hydrochloride IV over 8-9 hours on day -2.
TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes.
POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz SC QD starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an ANC of 0.5 x 10^9/L.
干预措施: Filgrastim-sndz (Biological)
Group 2 (melphalan hydrochloride, HSCT, filgrastim)
PREPARATIVE REGIMEN: Participants receive melphalan hydrochloride IV over 8-9 hours on day -2.
TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes.
POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz SC QD starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an ANC of 0.5 x 10^9/L.
干预措施: Melphalan Hydrochloride (Drug)
结局指标
主要结局
Optimal Dose and Schedule of Evomela Prior to Autologous Transplant.
时间窗: Within 30 days after the start of infusion
Dose limiting toxicity will be defined as grade 4 mucositis or any grade 4 or 5 non-hematologic or non-infectious toxicity occurring within 30 days from the start of infusion.
次要结局
- Progression-free Survival (PFS)(From the date of Evomela injection up to 1 year)
- Treatment Related Mortality (TRM).(At day 90 post-transplant)
- Number of Participants That Have Achieved Complete Response (CR).(At 90 days post-transplant)