Randomized Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Complete response proportion
研究概览
简要总结
This randomized phase II trial studies the side effects and how well melphalan hydrochloride works in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
详细描述
PRIMARY OBJECTIVES:
I. Identify whether targeting approximate (approx.) 3- or 5-days of severe neutropenia after exposure to a personalized melphalan hydrochloride (melphalan) dose results in best clinical outcome.
II. Measure melphalan-related toxicities in both 3-day and 5-day arms. III. Measure response per International Myeloma Working Group (IMWG). IV. Record overall survival (OS) and progression free survival (PFS).
SECONDARY OBJECTIVES:
I. To administer a test dose of melphalan and obtain test dose melphalan pharmacokinetics (PK) data from the first 33 patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have relapsed or refractory myeloma that fits or did fit IMWG diagnostic criteria for multiple myeloma; patients with AL amyloidosis and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) are excluded; measurable disease is not required
- •Patient undergoing autologous transplant as part of first line therapy
- •All races and ethnic groups are eligible for this study
- •Patients must also have an adequate autologous graft as defined as a cryopreserved peripheral blood stem cell (PBSC) graft containing > 2 x 10^6 CD34+ cells/kg patient weight
- •Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%) is required for eligibility; those patients with lower performance status based solely on bone pain secondary to multiple myeloma are eligible
- •Absolute neutrophil count (ANC) > 1000/uL
- •Platelet count > 50,000
- •Transfusion independent
- •Total bilirubin < 1.5 mg/dL
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x the institutional upper limit of normal
- •Left ventricular ejection fraction >= 40%
- •Carbon monoxide diffusing capability (DLCO) > 50% predicted
- •Forced expiratory volume in 1 second (FEV1) > 50% predicted
- •Forced vital capacity (FVC) > 50% predicted
- •Ability to understand and willingness to sign a written informed consent document
- •Females of childbearing potential (FCBP) must not be pregnant as per institutional standard; if no institutional standard exists, then patients must have a negative serum or urine pregnancy test prior to transplant; a female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
排除标准
- •Patients who are receiving any other anti-myeloma investigational agents
- •Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the preceding 6 months, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study; breastfeeding should be discontinued
- •Patients with a "currently active" second malignancy that, in the opinion of the principal investigator, will interfere with patient participation, increase patient risk, shorten survival to < 1 year, or confound data interpretation
- •Concurrent use of complementary or alternative medicines that in the opinion of the principal investigator would confound the interpretation of toxicities and/or antitumor activity of the study drug
研究组 & 干预措施
Arm I (melphalan hydrochloride for 3-day severe neutropenia)
Patients receive personalized dose of melphalan hydrochloride IV on day -2 for for predicted 3-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (melphalan hydrochloride for 3-day severe neutropenia)
Patients receive personalized dose of melphalan hydrochloride IV on day -2 for for predicted 3-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.
干预措施: Pharmacological Study (Other)
Arm II (melphalan hydrochloride or 5-day severe neutropenia))
Patients receive personalized dose of melphalan hydrochloride IV on day -2 for predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (melphalan hydrochloride or 5-day severe neutropenia))
Patients receive personalized dose of melphalan hydrochloride IV on day -2 for predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.
干预措施: Pharmacological Study (Other)
Arm II (melphalan hydrochloride or 5-day severe neutropenia))
Patients receive personalized dose of melphalan hydrochloride IV on day -2 for predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.
干预措施: Melphalan Hydrochloride (Drug)
Arm I (melphalan hydrochloride for 3-day severe neutropenia)
Patients receive personalized dose of melphalan hydrochloride IV on day -2 for for predicted 3-day duration of severe neutropenia and undergo standard of care autologous stem cell transplant on day 0.
干预措施: Melphalan Hydrochloride (Drug)
结局指标
主要结局
Complete response proportion
时间窗: At 90 days
Complete response will be defined as complete response + stringent complete response according to the International Myeloma Working Group Uniform response criterion. Will be calculated with an exact 95% confidence interval, both within arms and across arms.
次要结局
- Incidence of melphalan hydrochloride-related toxicities(Up to 3.5 years)
- Overall survival(time from randomization to death, assessed up to 3.5 years)
- Time to progression(Time from start of melphalan hydrochloride until the criteria for disease progression are met, assessed up to 3.5 years)
- Minimal residual disease negative proportions(up to 1 year)
- Progression free survival(Time from transplant to death, clinical relapse, progressive disease, and death in all treated patients, assessed up to 3.5 years)
- Time to biochemical relapse(Time from start of melphalan hydrochloride until the earliest of the following time points: progressive disease, clinical relapse, or relapse from complete response, assessed up to 3.5 years)
研究者
Ashley Rosko
Principal Investigator
Ohio State University Comprehensive Cancer Center