A Phase II Single-Center, Open-Label, Safety and Efficacy Study of Propylene Glycol-Free Melphalan Hydrochloride (Evomela) in AL Amyloidosis Patients Undergoing Autologous Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Number of Participants With Renal Dysfunction
研究概览
简要总结
This is a single arm, open label study designed to evaluate the safety and efficacy of propylene glycol-free melphalan hydrochloride in patients with AL amyloidosis. Treatment will be comprised of propylene glycol-free melphalan hydrochloride administered intravenously at a dose of 70-100 mg/m2/day on Days -3 and -2 as conditioning prior to autologous stem cell transplantation.
详细描述
After giving written informed consent, subjects will be evaluated for eligibility for enrollment in the study. Baseline evaluations will be performed as outlined in Section 7. Subjects who satisfy all inclusion and exclusion criteria will begin the study drug. Subjects will be monitored from the time of the medication administration until discharge from the transplant program for safety. Organ function and hematologic status will also be measured at 6 and 12 month follow-up visits.
Standard response criteria for AL amyloidosis hematologic and organ response will be used. Overall response rate will be measured and participants will be categorized into complete response, very good partial response, partial response and progressive disease. Progression free survival, organ response, and safety and tolerability of propylene glycol-free melphalan hydrochloride will be assessed.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Eastern Cooperative Oncology Group Performance Status 0-2
- •Histologic diagnosis of primary systemic (AL) amyloidosis based on:
- •Deposition of amyloid material by Congo red stain showing characteristic apple green birefringence AND
- •Evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum or urine by immunofixation electrophoresis AND/OR abnormal serum free light chain assay AND/OR clonal plasma cells in the bone marrow exam demonstrated by immunohistochemistry, flow cytometry, or in situ hybridization AND
- •Evidence of organ involvement
- •Eligible for treatment with high dose melphalan and stem cell transplantation per institutional guidelines
- •Ability to understand and willingness to sign informed consent
- •Pulmonary Function Test demonstrating a diffusion capacity of lung for carbon monoxide ≥ 50%
- •Left ventricular ejection fraction ≥40%
- •Systolic blood pressure >90 mm Hg (supine position)
- •Eastern Cooperative Oncology Group Performance status of 2 or better (unless patient is diagnosed with AL amyloidosis involving the gastrointestinal and peripheral/autonomic nervous systems, then performance status of 3 is acceptable)
排除标准
- •Previous high-dose melphalan and stem cell transplant
- •Previous total cumulative dose of oral melphalan > 300 mg
- •Cytotoxic chemotherapy within the previous 28 days
- •New York Heart Association ≥3
- •Decompensated or uncontrolled heart failure
- •Oxygen dependence
- •epidermal growth factor receptor < 30 ml/min
- •Active infection (i.e HIV, Hepatitis B or C)
- •Pregnancy or breastfeeding
- •Exposure to another investigational drug within 3-4 weeks prior to start of study treatment
- •Ongoing alcohol or drug addiction
- •Unable or unwilling to comply with the protocol
研究组 & 干预措施
Evomela
Propylene Glycol-Free Melphalan Hydrochloride (Evomela) administered intravenously at 70-100 mg/m2/day on Days -3 and -2 prior to autologous stem cell transplantation
干预措施: Propylene Glycol-Free Melphalan Hydrochloride (Drug)
结局指标
主要结局
Number of Participants With Renal Dysfunction
时间窗: 100 days
To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to renal dysfunction (was acute renal failure is defined as either a \>/=1 mg/dL increase in serum creatinine or a doubling of serum creatinine to \>/=1.5 mg/dL for at least 2 days.).
Number of Participants With Cardiac Dysfunction (New Arrhythmia)
时间窗: 100 days
To determine the safety profile of propylene glycol-free melphalan hydrochloride in the conditioning regimen prior to autologous stem cell transplantation in AL amyloidosis patients, including adverse events related to cardiac dysfunction (new arrhythmia).
次要结局
- Neutrophil Engraftment(3 weeks)
- Platelet Engraftment(100 days)
- Treatment Related Mortality(100 days)
- Hematologic Overall Response Rate(6 months)
- Organ Response(12 months)
- Participants With Peri-transplant Hospitalizations(100 days)