A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Time to Platelet Absolute Neutrophil Recovery (Engraftment)
研究概览
简要总结
This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells
详细描述
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).
-
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).
-
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:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: pharmacological study (Other)
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.
干预措施: tacrolimus (Drug)
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.
干预措施: sirolimus (Drug)
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.
干预措施: anti-thymocyte globulin (Biological)
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.
干预措施: fludarabine phosphate (Drug)
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.
干预措施: busulfan (Drug)
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.
干预措施: bortezomib (Drug)
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.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
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.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Time to Platelet Absolute Neutrophil Recovery (Engraftment)
时间窗: First 6 months post-transplant
Estimated using Kaplan-Meier method.
Treatment Related Mortality Defined as Death in Continuous or Complete Remission
时间窗: From the date of transplant to the date of death, assessed up to 6 months post transplant
Based on National Cancer Institute (NCI) CTCAE version 4.
Grade III and IV Non Hematologic Toxicities
时间窗: First 6 months post transplant
Based on NCI CTCAE version 4.
Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
时间窗: 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.
次要结局
- Incidence of Myeloma Progression(Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant)
- Incidence of SOS(Up to 2 years post transplant)
- Incidence and Severity of Chronic GVHD(Up to 2 years post transplant)
- Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation(Weekly to day 100)
- Incidence of Transplant Related Mortality and Morbidity(Up to 2 years post transplant)
- Incidence of TTP(Up to 2 years post transplant)
- Overall Survival(Up to 2 years post transplant)
- Progression Free Survival(From the day of transplant to progression, death, or last contact, assessed up to 2 years)
- Recovery of T-cell, B Cell and NK Cell Phenotypes(Days 30, 60, 90, and at 6 months after transplant)
研究者
Zaid Al-Kadhimi
Principal Investigator
Barbara Ann Karmanos Cancer Institute