A Phase II Study of V-BEAM (Bortezomib, Carmustine, Etoposide, Cytarabine, and Melphalan) as Conditioning Regimen Prior to Second Autologous Stem Cell Transplantation for Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Complete Response Rate (Complete Response + Stringent Complete Response)
研究概览
简要总结
BEAM regimen (BCNU, etoposide, cytarabine, and melphalan) is the most commonly used conditioning regimen for relapsed/refractory lymphoma patients needing autologous stem cell transplantation. Since these components are all effective in myeloma and bortezomib has shown promising results in the transplant setting, here the investigators propose a phase II study to investigate the combination of bortezomib and BEAM as a new conditioning regimen for patients who relapse or progress after the first autologous transplantation and for whom a second autologous transplant is considered.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have a histologically confirmed diagnosis of multiple myeloma.
- •Patient must have received a prior autologous stem cell transplantation with melphalan conditioning for multiple myeloma with subsequent disease progression and repeat autologous stem cell transplantation is deemed appropriate by the treating physicians.
- •Patient must receive induction chemotherapy including 2 to 4 cycles of anti-myeloma therapy including bortezomib, with or without immune modulating agents and/or corticosteroids, Completion of induction therapy will occur within 30 days of first study drug dose.
- •Patient must have ≥ 2x106/kg CD34+ autologous stem cells available for transplantation.
- •Patient must be ≥ 18 years of age.
- •Patient must have life expectancy of greater than 6 months.
- •Patient must have an ECOG performance status ≤ 2 or Karnofsky performance status ≥ 60% (see Appendices A and B)
- •Patient must have normal bone marrow and organ function as defined below within 14 days prior to first study drug dose (conditioning regimen):
- •Absolute neutrophil count ≥500/mm3
- •Platelets ≥ 50,000/mm3
- •Hemoglobin ≥ 8 g/dl
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- •Creatinine clearance (Appendix C) ≥30 mL/min/1.73m2
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- •Patient must be able to understand and willing to sign an IRB approved written informed consent document.
排除标准
- •Patient must not be refractory to induction therapy. Refractory is defined as disease progression while on therapy or within 30 days following completion of therapy.
- •Patient must not have had disease progression requiring active treatment within 12 months of previous autologous stem cell transplant. Maintenance therapy is not considered active treatment.
- •Patient must not have peripheral neuropathy ≥ grade 3 based on NCI CTCAE v 4.0 (Appendix D).
- •Patient must not be receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
- •Patient must not have another concurrent malignancy requiring treatment.
- •Patient must not be receiving any other investigational agents within 14 days prior to the first dose of study drug.
- •Patient must not have known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, carmustine, etoposide, cytarabine, and melphalan, or other agents used in the study.
- •Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patient must not be pregnant and/or breastfeeding.
- •Inclusion of Women and Minorities
- •Both men and women and members of all races and ethnic groups are eligible for this trial.
研究组 & 干预措施
V-BEAM + Stem Cell Infusion
Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0
干预措施: Bortezomib (Drug)
V-BEAM + Stem Cell Infusion
Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0
干预措施: Carmustine (Drug)
V-BEAM + Stem Cell Infusion
Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0
干预措施: Etoposide (Drug)
V-BEAM + Stem Cell Infusion
Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0
干预措施: Cytarabine (Drug)
V-BEAM + Stem Cell Infusion
Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0
干预措施: Melphalan (Drug)
V-BEAM + Stem Cell Infusion
Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0
干预措施: Stem cell infusion (Procedure)
结局指标
主要结局
Complete Response Rate (Complete Response + Stringent Complete Response)
时间窗: Day +100
Defined by the International Myeloma Working Group (IMWG) criteria
次要结局
- Overall Response Rate (ORR)(3 months following Day +100 visit)
- Number of Participants With Overall Survival (OS)(Median follow-up of 6 months (range: 6-12 months))
- Time to Platelet Engraftment After V-BEAM.(Day +100)
- Very Good Partial Response Rate (VGPR+nCR+sCR+CR)(Day +100)
- Time to Neutrophil Engraftment After V-BEAM.(Day +100)
- Number of Participants With Progression-free Survival (PFS)(Median follow-up of 6 months (range: 6.0-12.0 months))
- Treatment Related Mortality (TRM) of V-BEAM(Day +100)
- Toxicity of V-BEAM(30 days after end of treatment / Day +100)