High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant
A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.
研究概览
地位
详细说明
PRIMARY OBJECTIVES:
I. To determine time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20X 109^/L for 3 consecutive days).
2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).
3. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).
SECONDARY OBJECTIVES:
I. Incidence of myeloma progression in this high risk group of patients.
II. Incidence of transplant related mortality and morbidity.
III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).
IV. Incidence and severity of chronic GVHD.
V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.
I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post transplant.
VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.
GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.
After completion of study treatment, patients are followed up for up to 2 years.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Michigan
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Detroit、Michigan、美国、48201
- Barbara Ann Karmanos Cancer Institute
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Ability to provide informed consent
- Karnofsky Performance Status (KPS) >= 70
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor
- High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria:
- Progressive disease after autologous transplant. No less than 3 months post auto transplant
- Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib
- Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women
Exclusion Criteria:
- Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason
- Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason
- Patient with history of allergy to boron, mannitol, or bortezomib
- Creatinine clearance (CrCl) =< 50 ml/min
- Ejection Fraction < 50%
- Diffusion capacity of carbon monoxide (DLCO) < 50% predicted
- Forced expiratory volume in 1 second (FEV1) < 50% predicted
- Forced vital capacity (FVC) < 50% predicted
- Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator
- Liver enzymes > 3 times upper limit normal
- Bilirubin > 2 mg/dl (except Gilbert's disease)
- International normalized ratio (INR) > 2
- Any previous history of liver failure, hepatitis, or cirrhosis
- Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection
- Grade > I neuropathy
- Women who are pregnant or lactating
- Current or history of alcohol or drug abuse
- Use of other investigational agents within 30 days of enrollment to this study
- Any patient with ascites
- Any patient on home oxygen
- Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 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：Treatment (chemotherapy, enzyme inhibitor)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. |
相关研究
鉴于IV
其他名称：
相关研究
其他名称：
鉴于IV
其他名称：
给定采购订单
其他名称：
鉴于IV
其他名称：
鉴于IV
其他名称：
接受同种异体 HSCT
鉴于IV
其他名称：
|
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 |
|---|---|---|
|
Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
大体时间：First 6 months post-transplant
|
Graded using the Glucksberg scale.
Proportions and confidence intervals will be estimated.
Estimated using binary proportion estimates as well as competing risk method.
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First 6 months post-transplant
|
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Time to Platelet Absolute Neutrophil Recovery (Engraftment)
大体时间：First 6 months post-transplant
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Estimated using Kaplan-Meier method.
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First 6 months post-transplant
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Treatment Related Mortality Defined as Death in Continuous or Complete Remission
大体时间：From the date of transplant to the date of death, assessed up to 6 months post transplant
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Based on National Cancer Institute (NCI) CTCAE version 4.
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From the date of transplant to the date of death, assessed up to 6 months post transplant
|
|
Grade III and IV Non Hematologic Toxicities
大体时间：First 6 months post transplant
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Based on NCI CTCAE version 4.
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First 6 months post transplant
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
总生存期
大体时间：移植后长达 2 年
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移植后长达 2 年
|
|
Incidence of Myeloma Progression
大体时间：Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
|
Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
|
|
Incidence of Transplant Related Mortality and Morbidity
大体时间：Up to 2 years post transplant
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Up to 2 years post transplant
|
|
Incidence of TTP
大体时间：Up to 2 years post transplant
|
Up to 2 years post transplant
|
|
Incidence of SOS
大体时间：Up to 2 years post transplant
|
Up to 2 years post transplant
|
|
Incidence and Severity of Chronic GVHD
大体时间：Up to 2 years post transplant
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Up to 2 years post transplant
|
|
Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation
大体时间：Weekly to day 100
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Weekly to day 100
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Progression Free Survival
大体时间：From the day of transplant to progression, death, or last contact, assessed up to 2 years
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From the day of transplant to progression, death, or last contact, assessed up to 2 years
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Recovery of T-cell, B Cell and NK Cell Phenotypes
大体时间：Days 30, 60, 90, and at 6 months after transplant
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Days 30, 60, 90, and at 6 months after transplant
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合作者和调查者
调查人员
- 首席研究员：Zaid Al-Kadhimi、Barbara Ann Karmanos Cancer Institute
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 2011-151
- NCI-2012-00120 (注册表标识符：CTRP (Clinical Trial Reporting Program))
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