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Busulfan, Melphalan, Escalating Carfilzomib Conditioning Auto Stem Cell Transplantation for Multiple Myeloma (MM) (BuMelCarAuto)

2021年4月23日 更新者：Patrick Stiff、Loyola University

Phase I/II Study Utilizing High Dose Busulfan and Melphalan With Escalating Carfilzomib as Conditioning in Autologous Peripheral Blood Stem Cell Transplantation for Patients With Multiple Myeloma

In this protocol, the investigators hypothesize that the combination of intravenous busulfan and melphalan with carfilzomib will be an effective preparative regimen with acceptable toxicity for participants with multiple myeloma who are candidates for autologous stem cell transplantation. To test this hypothesis, the investigators designed a phase I/II trial combining IV busulfan 130 mg/m2 plus melphalan 140 mg combined with escalating doses of carfilzomib ranging from 20 mg/m2 to 45 mg/m2. These results will be compared with the center's historical controls of participants treated with melphalan, busulfan and bortezomib.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

Participants enrolled in this study protocol will receive daily intravenous (IV) infusions of carfilzomib for a total of 4 days (Day-9, -8 and Days -2, -1). The first two daily infusions will be given at a fixed dose of 20 mg/m2 and the final two doses will be escalated from the standard dose of 27 mg/m2 to 56 mg/m2 in a Phase I design, based on toxicity. The busulfan will be administered for 2 days over 3 hours from D-7, -6, at 130 mg/m2 . This dose was found to be safe and equivalent to the standard daily dose of 3.2 mg/kg. The 3rd and 4th daily doses of IV Busulfan will be adjusted in order to yield a systemic plasma drug exposure represented by a daily area under the plasma concentration versus time curve (AUC) of approximately 5,000 millimoles-minute per dose (mM-min). These targeted plasma concentration of IV busulfan will be based on pharmacokinetics studies performed during the first day of IV busulfan. Melphalan will be given at a dose of 140 mg/m2 on Day -3. Each cohort will start with a goal of accruing three patients to determine the dose limiting toxicity.

研究类型

介入性

注册 (预期的)

36

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 美国
    • Illinois
      • Maywood、Illinois、美国、60153
        • 招聘中
        • Loyola University Medical Center
        • 接触：
          • Mary Lee, RN
          • 电话号码：708-327-2241
          • 邮箱：mlee@luc.edu
        • 接触：

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Participants must be greater than or equal to 18 years of age.
  • Participants must have been diagnosed with multiple myeloma in a first or subsequent remission and have undergone a successful pre-transplant work up and are otherwise eligible for an autotransplant with a busulfan/melphalan preparative regimen at Loyola University Medical Center.
  • Participants may receive this preparative regimen if in first or subsequent remission. Participants may enter if they have received a prior autologous stem cell transplant and this therapy produced a remission that lasted greater than 18 months before progression of disease. Participants who have undergone prior allogeneic transplantation are excluded.
  • All participants must have responsive disease as defined by a Partial Response or greater to most recent conventional regimen.
  • Participants receiving prior carfilzomib will be eligible for inclusion provided they demonstrated responsive disease to this agent and either had a remission that lasted greater than 6 months after its discontinuance, or if in remission after a carfilzomib containing regimen administered to qualify for transplant.
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) less than or equal to 2.
  • Acceptable heart function test.

Exclusion Criteria:

  • Participants must not have below normal kidney function.
  • Participants must not have below normal liver function.
  • Participants must not have active bacterial, fungal, or viral infection.
  • Participants must not have severe lung function.
  • Participants must not have Grade 2 or greater peripheral neuropathy.
  • Participants must not have uncontrolled hypertension.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Carfilzomib IV at dose: 20 mg/m2
The participants will receive Carfilzomib IV at dose: 20 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and Granulocyte-Colony stimulating factor (G-CSF) given daily until engraftment occurs.
药品：Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
其他名称：
  • Kyprolis
药品：Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 白消安
药品：Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 阿尔克兰
实验性的：Carfilzomib IV at dose: 27 mg/m2
The participants will receive Carfilzomib IV at dose: 27 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
药品：Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
其他名称：
  • Kyprolis
药品：Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 白消安
药品：Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 阿尔克兰
实验性的：Carfilzomib IV at dose: 36 mg/m2
The participants will receive Carfilzomib IV at dose: 36 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
药品：Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
其他名称：
  • Kyprolis
药品：Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 白消安
药品：Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 阿尔克兰
实验性的：Carfilzomib IV at dose: 45 mg/m2
The participants will receive Carfilzomib IV at dose: 45 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
药品：Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
其他名称：
  • Kyprolis
药品：Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 白消安
药品：Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 阿尔克兰
实验性的：Carfilzomib IV at dose: 56 mg/m2
The participants will receive Carfilzomib IV at dose: 56 mg/m2 on days -9 and -8 over 30 minutes. The participant will receive Busulfan IV over 3 hours every 24 hours for a total of 4 doses from Day -6 to Day -3 and Melphalan IV over 15-30 minutes for one dose on day -3.The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs.
药品：Carfilzomib
Carfilzomib is an anti-cancer drug acting as a selective proteasome inhibitor that is used to treat Multiple Myeloma.
其他名称：
  • Kyprolis
药品：Busulfan IV
Busulfan is an anti-cancer drug acting as a bifunctional alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 白消安
药品：Melphalan IV
Melphalan is an anti-cancer drug acting as alkylating agent that is used to treat Multiple Myeloma.
其他名称：
  • 阿尔克兰

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
36 participants evaluated for safety with treatment-related adverse events and grading by using CTCAE v4.0.
大体时间：3 years
To determine the maximal tolerated dose of carfilzomib when added to busulfan and melphalan as a preparative regimen for high dose therapy with autologous hematopoietic transplantation for patients with multiply myeloma.
3 years
36 participants evaluated for tolerability with treatment-related adverse events and grading by using CTCAE v4.0.
大体时间：3 years
To determine the maximal tolerated dose of carfilzomib when added to busulfan and melphalan as a preparative regimen for high dose therapy with autologous hematopoietic transplantation for patients with multiply myeloma.
3 years

次要结果测量

结果测量
措施说明
大体时间
36 participants evaluated for response to treatment by testing blood for multiple myeloma levels.
大体时间：100 days
To evaluate complete, very good partial, partial and stable disease response rate for both clinical and biologic endpoints.
100 days
36 participants evaluated for progression by testing blood for multiple myeloma levels.
大体时间：3 years
Progression Free Survival
3 years
36 participants evaluated for overall survival by clinical visit or contact by phone.
大体时间：3 years
Overall Survival
3 years
36 participants evaluated for absolute neutrophil count by testing white blood cells levels.
大体时间：100 days
Days to neutrophil engraftment: Absolute neutrophil count > 500/microliter
100 days
36 participants evaluated for platelet engraftment by testing platelet count in blood cells.
大体时间：100 days
Days to platelet engraftment: platelet count > 20,000/microliter untransfused
100 days
36 participants evaluated by oral exam to assess mucositis events and grading levels by using CTCAE v4.0.
大体时间：100 days
Mucositis: CTCAE v 4.0 grade and severity
100 days
36 participants evaluated by the liver to assess Veno-occlusive disease and grading levels by using CTCAE v4.0.
大体时间：100 days
Veno-occlusive disease
100 days
36 participants evaluated by a physical exam to assess peripheral neuropathy and grading by using CTCAE v4.0.
大体时间：3 years
Peripheral neuropathy greater than or equal to CTCAE V 4.0 Grade 3
3 years
36 participants evaluated for response to treatment by testing urine for multiple myeloma levels.
大体时间：100 days
To evaluate complete, very good partial, partial no stable disease response rate for both clinical and biologic endpoints
100 days
36 participants evaluated for progression by testing urine for multiple myeloma levels.
大体时间：3 years
Progression Free Survival
3 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Loyola University

合作者

Amgen

调查人员

  • 首席研究员：Patrick Stiff, MD、Loyola University

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2019年5月22日

初级完成 (预期的)

2022年11月1日

研究完成 (预期的)

2023年11月1日

研究注册日期

首次提交

2018年10月17日

首先提交符合 QC 标准的

2019年1月3日

首次发布 (实际的)

2019年1月8日

研究记录更新

最后更新发布 (实际的)

2021年4月26日

上次提交的符合 QC 标准的更新

2021年4月23日

最后验证

2021年4月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 209274

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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条件

罕见疾病

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