20150288 A Phase 2 Open-label Study Investigating the Safety and Efficacy of Blinatumomab After Frontline R-Chemotherapy in Adult Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Participants With Treatment-Emergent (Blinatumomab) Adverse Events
研究概览
简要总结
A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL.
详细描述
The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Clinically relevant central nervous system (CNS) pathology requiring treatment such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
- •Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab
- •Current autoimmune disease or history of autoimmune disease with potential of CNS involvement
- •Subject has active infection requiring systemic therapy
- •Prior anti-CD19 therapies
- •Known infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus
- •History of other malignancy within the past 3 years with the following exceptions:
- •Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
- •Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease
- •Adequately treated cervical carcinoma in situ without evidence of disease
- •Adequately treated breast ductal carcinoma in situ without evidence of disease
- •Prostatic intraepithelial neoplasia without evidence of prostate cancer
- •Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
- •Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
- •Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge.
- •History/evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- •Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab.
- •Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.
研究组 & 干预措施
Blinatumomab
Blinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time.
An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days.
There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death.
干预措施: Blinatumomab (Drug)
Blinatumomab
Blinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time.
An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days.
There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death.
干预措施: Investigator's Choice Chemotherapy (Drug)
Blinatumomab
Blinatumomab was administered as a continuous intravenous (IV) infusion. Cycle 1 was 12 weeks (84 days) in duration with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, 112 µg/day for 6 weeks, followed by a 4-week treatment free time.
An optional 4-week Cycle 2 of blinatumomab was available for participants whose disease did not progress, with step dosing of 9 µg/day for 7 days, 28 µg/day for 7 days, and 112 µg/day for 14 days.
There was a safety follow-up for 30 days. And a long-term follow-up of up to 8 months for a maximum of 1 year from first dose of blinatumomab or until participant death.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Participants With Treatment-Emergent (Blinatumomab) Adverse Events
时间窗: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days
Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab investigative product (IP) treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.
Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment
时间窗: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days
Overall incidence and severity of treatment-emergent adverse events deemed by investigators to be related to blinatumomab treatment. Severity was graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and based on the scale: Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death.
次要结局
- Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period(Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2)
- Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT)(Day 1 up to 14.5 months)
- Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1(Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle)
- Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1(Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle)
- Kaplan-Meier Estimates for Duration of Response(The median (range) follow-up time was 11.5 (8.2, 14.5) months)
- Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab(The median (range) follow-up time was 12.0 (10.7, 14.5) months.)
- Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period(Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2)
- Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab(The median (range) follow-up time was 12.0 (8.2, 14.5))