A Phase I/II Trial of Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed or Refractory Multiple Myeloma: Hoosier Cancer Research Network MM08-141
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 32
- 试验地点
- 7
- 主要终点
- Phase II : Overall Response Rate
研究概览
简要总结
This is an open label phase I/II trial to determine the safety and the biologic activity of the bendamustine, bortezomib and pegylated liposomal doxorubicin combination.
详细描述
Phase I component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV over 1 hour, Day 4 Bendamustine escalating cohorts IV over 1 hour, Days 1 and 4 1 Cycle = 28 days
Phase II component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV over 1 hour, Day 4 Bendamustine at MTD IV over 1 hour, Days 1 and 4 Filgrastim (if defined in MTD) 5 µg/kg/day SC, Starting day 6 until neutrophil recovery to ANC >1000
1 Cycle = 28 days; Patients will continue treatment for a total of up to 8 cycles.
ECOG Performance Status: 0-2
Hematopoietic:
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
- •A histologically established diagnosis of multiple myeloma with evidence of relapse or refractory disease.
- •Must have a detectable serum or urine M-Protein by protein electrophoresis that is at least 500 mg/dL (serum) or 1 gm/24 hours (urine), respectively, or serum free light chain level >100 mg/l for the involved free light chain.
- •Must have received at least one (1) prior line of systemic treatment that has included either lenalidomide or thalidomide.
- •Must be willing to provide correlative blood samples.
排除标准
- •Must not have received an excessive cumulative dose of anthracycline
- •No ≥ grade 2 peripheral neuropathy.
- •No cytotoxic chemotherapy within 30 days prior to registration for protocol therapy.
- •No autologous stem cell transplant within 6 months prior to registration for protocol therapy
- •No prior radiation therapy to > 25% of bone marrow forming bones (i.e., pelvis) within 30 days prior to registration for protocol therapy. See Study Procedures Manual to calculate percent of prior radiation.
- •No current corticosteroid therapy in doses greater than 10 mg daily of prednisone (or equivalent) if given for management of co-morbid conditions.
- •No known central nervous system involvement by myeloma.
- •No poorly controlled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled diabetes, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social climate that in the opinion of the investigator would limit compliance with study requirements.
- •No patients known to be positive for HIV, or active Hepatitis A, B, or C.
- •No major surgery within 30 days prior to registration for protocol therapy. Placement of a venous access device within 30 days prior to registration for protocol therapy is allowed.
研究组 & 干预措施
Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
干预措施: Bortezomib (Drug)
Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
干预措施: Bendamustine (Drug)
Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
干预措施: Doxorubicin (Drug)
Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
干预措施: Filgrastim (Drug)
结局指标
主要结局
Phase II : Overall Response Rate
时间窗: From C1D1 up to a maximum of 52 months or until death
Overall response rate (CR+PR) of bendamustine in association with bortezomib and pegylated liposomal doxorubicin was assessed in patients with relapsed or refractory Multiple Myeloma. Per modified International Myeloma Working Group criteria: Complete Response (CR) : Negative for monoclonal protein by immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow ; PR : 50% or more reduction in serum M-protein and 90% or more reduction in urine M-protein or to \<200 mg/24hours or a 50% or more reduction in free light chain level ; Overall Response (OR) = CR +PR.
Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.
时间窗: From C1D1 up to a maximum of 7 months or until death
In the first phase, MTD of bendamustine was determined in combination with bortezomib and pegylated liposomal doxorubicin to gain a better idea of safe dosing before proceeding with the second phase to assess efficacy. Assuming myelosuppression being a dose-limiting effect that could have been overcome with growth factor support, MTD of the combination with myeloid growth factor support was also tested.
次要结局
- Phase II: Overall Survival(From C1D1 up to a maximum of 54 months or until death)
- Phase I & Phase II : Toxicity of Treatment Regimen(From C1D1 until death or up to a maximum of 54 months)
- Phase II: Progression-free Survival (PFS)(From C1D1 up to a maximum of 54 months until death)
- Phase II: Duration of Survival(From C1D1 up to a maximum of 52 months)
- Phase II : Time to Progression(From C1D1 up to a maximum of 54 months or until death)
研究者
Sherif Farag, MB, BS
Sponsor-Investigator
Hoosier Cancer Research Network