NCT01009840已完成2 期
A Phase 2a Study of Once Daily Intravenous Busulfan With Bortezomib, Followed by an Autologous Hematopoietic Stem Cell Transplant (HSCT) in Subjects With Relapsed Multiple Myeloma After Prior Autologous HSCT
Otsuka Pharmaceutical Development & Commercialization, Inc.13 个研究点 分布在 2 个国家目标入组 30 人开始时间: 2010年5月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Percentage of Participants With Overall Disease Response at Month 6
研究概览
简要总结
Study for the outcome and safety of individualized busulfan dosing with bortezomib for patients preparing for a second stem cell transplant to treat multiple myeloma.
详细描述
Evaluation of six-month response in relapsed multiple myeloma subjects, who have had a prior autologous HSCT (greater than one year previously) receiving an IV busulfan-based conditioning regimen with the combination of pharmacokinetic (PK)-guided IV busulfan dosing and bortezomib, followed by a second autologous HSCT.
Assessment of the safety profile of this conditioning regimen will also be completed.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years, inclusive.
- •Subjects must have multiple myeloma which requires treatment for relapsed disease and are eligible for the planned autologous HSCT.
- •Subjects must have had one previous autologous HSCT, at least one year prior to the planned autologous HSCT in this study.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
- •Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all women of child-bearing potential.
- •Subjects who are surgically sterile (ie, have undergone orchidectomy or hysterectomy); female subjects who have been postmenopausal for at least 12 consecutive months; or subjects who agree to remain abstinent or to practice double-barrier forms of birth control from trial screening through 30 days (for females) and 90 days (for males) from the last dose of the investigational medicinal product (IMP). If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), birth control pill, birth control implant, condom, or sponge with spermicide.
- •Subjects in whom the minimum stem cell dose of 2.0 x 10^6 cluster of differentiation 34 (CD34)+ cells/kg has been collected.
- •Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Principal Investigator, to comply with all requirements of the study.
排除标准
- •Prior treatment history of allogeneic HSCT for any medical reason, not limited to myeloma treatment.
- •Prior treatment history of more than one autologous HSCT or high-dose chemotherapy with stem cell rescue for any medical reason, not limited to myeloma treatment.
- •Prior treatment with busulfan or gemtuzumab ozogamicin for any reason.
- •Presence of a t(4;14) or p53 gene deletion as determined by fluorescence in situ hybridization (FISH) during the screening process or documented t(4; 14) or p53 gene deletion obtained during a time of active disease by any method.
- •Systemic amyloidosis.
- •Known allergy to boron or any components of bortezomib.
- •Left ventricular ejection fraction (LVEF) < 45% as measured by either multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) performed within 75 days prior to day of busulfan test dose. If cyclophosphamide was used for stem cell harvest, an ECHO or MUGA must be done prior to enrollment to confirm adequate cardiac function.
- •Uncontrolled arrhythmia or symptomatic cardiac disease at the time of screening.
- •Symptomatic pulmonary disease, based on Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) < 50% of predicted (corrected for hemoglobin) measured within 75 days prior to day of busulfan test dose.
- •Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 3 x the upper limit of normal (ULN),
- •History of elevated total serum bilirubin >2 mg/dL that had been caused by previous chemotherapy at any point, or total bilirubin > 2.0 mg/dL at the time of screening with the exception of Gilbert's disease.
- •Hepatic synthetic dysfunction evident International Normalized Ratio (INR) ≥ 2.0 at the time of screening.
- •Any previous history of fulminant liver failure, cirrhosis, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, and symptomatic biliary disease.
- •Prior total body irradiation therapy or radiation therapy directly applied to the liver.
- •Known history of or current hepatitis B, hepatitis C, HIV, or uncontrolled active infection of any kind at the time of test dose. If serology antibody studies are positive, a quantitative polymerase chain reaction (PCR) must be completed to confirm lack of active infection.
- •Serum creatinine >2.0 mg/dL at the time of Screening.
- •≥ Grade 1 neuropathy with pain, or > Grade 2 neuropathy without pain (subjects with neuropathy caused by a previous regimen that is recovered to ≤ Grade 2 and stable without pain may be included).
- •Women who are pregnant or lactating.
- •Current or history of drug and/or alcohol abuse.
- •Use of other investigational therapies within 30 days
研究组 & 干预措施
IV busulfan
Experimental
Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the PK-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to HSCT.
干预措施: Autologous Hematopoietic Stem Cell Transplant (HSCT) (Procedure)
IV busulfan
Experimental
Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the PK-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to HSCT.
干预措施: IV busulfan (Drug)
IV busulfan
Experimental
Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the PK-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to HSCT.
干预措施: bortezomib (Drug)
结局指标
主要结局
Percentage of Participants With Overall Disease Response at Month 6
时间窗: 6 Months
The percentage of participants reported in each disease category by International Myeloma Working Group (IMWG) uniform response criteria for Multiple Myeloma 6 months after autologous Hematopoietic stem cell transplant. Overall Disease Response categories were: \[stringent Complete Response (sCR)=CR + normal Free Light Chain (FLC) ratio + absence of clonal cells in bone marrow\], \[Complete Response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow\], \[Very Good Partial Response (VGPR)=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein + urine M-protein level \<100 mg/24 hour\], \[Partial Response (PR)=≥50% reduction of serum M-protein and reduction in 24 hour urine M-protein by ≥90% or to \<200 mg per 24 hour\], \[Stable Disease (SD)=Not meeting criteria for CR, VGPR, PR or progressive disease\] or \[Progressive Disease (PD)\].
次要结局
- Overall Survival(6 Months)
- Percentage of Participants With Transplant-Related Mortality(6 Months)
- Percent Change in IV Busulfan Dose(Baseline (Day -12 to -9), Day -5)
- Progression-free Survival(6 Months)
- Percentage of Participants With Overall Survival Events(6 Months)
- Percentage of Participants With Progression-free Survival Events(6 Months)
- Ratio Area Under Curve (AUC)/Target AUC(Baseline (Day -12 to -9), Day -5)
- Percent Difference Between Area Under Curve (AUC) and Target AUC(Baseline (Day -12 to -9), Day -5)
- Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria(6 Months)
研究者
研究点 (13)
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Leukemia/LymphomaStage IIB Mycosis Fungoides/Sezary SyndromeStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult T-cell Leukemia/LymphomaStage III Childhood Lymphoblastic LymphomaStage III Grade 2 Follicular LymphomaAdult Grade III Lymphomatoid GranulomatosisAngioimmunoblastic T-cell LymphomaChildhood Grade III Lymphomatoid GranulomatosisChildhood Immunoblastic Large Cell LymphomaContiguous Stage II Grade 1 Follicular LymphomaContiguous Stage II Grade 2 Follicular LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaNoncontiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaNoncontiguous Stage II Adult Lymphoblastic LymphomaNoncontiguous Stage II Grade 3 Follicular LymphomaNoncontiguous Stage II Mantle Cell LymphomaNoncontiguous Stage II Marginal Zone LymphomaPeripheral T-cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III 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