A Phase II Study of Pembrolizumab (MK-3475) in Subjects With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) or Relapsed or Refractory Richter Syndrome (rrRS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 主要终点
- Objective Response Rate (ORR) Based on International Working Group (IWG) Response Assessment Criteria Per Independent Central Review
研究概览
简要总结
In this study, participants with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) or relapsed or refractory Richter Syndrome (rrRS) will receive pembrolizumab (MK-3475). The efficacy of pembrolizumab in the treatment of rrPMBCL and rrRS will be evaluated. The primary study hypothesis is that intravenous (IV) administration of single agent pembrolizumab to the rrPMBCL cohort will result in an Objective Response Rate (ORR) of greater than 15% using the International Working Group (IWG) response criteria (Cheson, 2007) by independent central review.
Effective with Protocol Amendment 04, enrollment into the rrRS cohort was closed.
详细描述
Treatment with pembrolizumab will continue for a maximum of 35 administrations (approximately 2 years) or until documented disease progression by investigator assessment, unacceptable adverse event(s) (AEs), intercurrent illness that prevents further administration of treatment, participant withdraws consent, pregnancy of the participant, noncompliance with study treatment or procedure requirements, or administrative reasons.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Primary mediastinal large B-cell lymphoma (PMBCL):
- •Diagnosis of relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) AND
- •Has relapsed after autologous stem cell transplant (auto-SCT) or has failed to achieve a Complete Response or Partial Response within 60 days of auto-SCT. Participants may have received intervening therapy after auto-SCT for relapsed or refractory disease, in which case they must have relapsed after or be refractory to their last treatment OR
- •For participants who are ineligible for auto-SCT, has received at least ≥2 lines of prior therapy and has failed to respond to or relapsed after their last line of treatment. For participants who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment
- •Previously exposed to rituximab as part of prior lines of treatment
- •Richter syndrome (RS):
- •Pathologic diagnosis per local institutional review of RS that transformed from chronic lymphocytic leukemia (CLL)
- •Relapsed or refractory Richter syndrome and has received ≥1 previous treatment for RS
- •All Participants:
- •Radiographically measurable disease
- •Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- •Life expectancy >3 months
- •Adequate organ function
- •Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug
- •Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug
排除标准
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug
- •Is receiving systemic steroid therapy <3 days before the first dose of study drug or receiving any other form of immunosuppressive medication
- •Prior monoclonal antibody within 4 weeks prior to study Day 1 (2 weeks for RS participants) or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier (2 weeks for RS participants)
- •Prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study Day 1 or prior radiation therapy within 4 weeks prior to study Day 1
- •Allogeneic hematopoietic stem cell transplantation within the last 5 years.
- •Has a known additional malignancy (except underlying CLL for RS) that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- •Known clinically active central nervous system involvement
- •Active autoimmune disease requiring systemic treatment in past 2 years
- •History of (non-infectious) pneumonitis that required steroids, or current pneumonitis
- •Active infection requiring intravenous systemic therapy
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study drug
- •Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- •Known human immunodeficiency virus (HIV), or Hepatitis B or C
- •Has received a live vaccine within 30 days prior to first dose of study drug
结局指标
主要结局
Objective Response Rate (ORR) Based on International Working Group (IWG) Response Assessment Criteria Per Independent Central Review
时间窗: Up to approximately 27 months (Database Cutoff: 28MAY2019)
The ORR was assessed by independent central review utilizing the International Working Group \[IWG\] response assessment criteria per Cheson 2007 of pembrolizumab in participants with rrPMBCL. For participants with rrRS, IWG criteria with special considerations for RS was used for progression. The ORR was defined as the percentage of participants who had a response (complete response, CR or partial response, PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data were considered non-responders. In the rrPMBCL cohort, an exact binomial test was conducted versus a fixed historical control rate. For the rrPMBCL cohort, the ORR was estimated as well as a 95% 2-sided exact confidence interval (CI) using the Clopper-Pearson method whereas the rrRS cohort was estimated with a 90% 2-sided CI.
次要结局
- Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Investigator Assessment(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Overall Survival (OS)(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 30 months (Up to 90 days after last dose of study treatment) (Database Cutoff Date: 28MAY2019))
- Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Investigator Assessment(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- ORR Based on IWG Response Assessment Criteria by Investigator Assessment(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Duration of Response (DOR) Based on IWG Response Assessment Criteria by Investigator Assessment in Participants With Responses(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Duration of Response (DOR) Based on IWG Response Assessment Criteria by Independent Central Review in Participants With Responses(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Independent Central Review(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Independent Central Review(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))
- Number of Participants Who Discontinued Study Drug Due to an AE(Up to approximately 27 months (Database Cutoff Date: 28MAY2019))