A Phase 1 Clinical Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (KEYNOTE-A33)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 9
- 主要终点
- Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review
研究概览
简要总结
The purpose of this study is to evaluate the objective response, safety, and tolerability of pembrolizumab in Japanese participants who have refractory primary mediastinal large B-cell lymphoma.
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
- •Diagnosis of Primary mediastinal B-cell lymphoma (PMBCL)
- •Relapsed or refractory PMBCL and:
- •Relapsed after auto-stem cell transplantation (SCT) or have failed to achieve a complete response (CR) or partial response (PR) within 60 days of auto-SCT; or
- •For participants who are ineligible for auto-SCT, has received at least ≥ 2 lines of prior therapy and have 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
- •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
- •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, OR must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
- •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 OR must be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
排除标准
- •Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137])
- •Received chimeric antigen receptor (CAR) T-cell therapy
- •Prior monoclonal antibody or radiation therapy within 4 weeks prior to the first dose of study intervention; OR received prior chemotherapy or targeted small molecule therapy within 2 weeks prior to the first dose of study intervention; OR has not recovered from adverse events due to a previously administered agent above. Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study
- •Major surgery within 3 weeks prior to first dose of study intervention
- •Received a live vaccine within 30 days prior to the first dose of study drug
- •Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention Participants in the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, that have undergone potentially curative therapy
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •History of (non-infectious) pneumonitis that required steroids, or current pneumonitis
- •Active infection requiring systemic therapy
- •History of human immunodeficiency virus (HIV) or Hepatitis B
- •Active Hepatitis C virus infection
- •Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
- •Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
- •Allogeneic hematopoietic stem cell/solid organ transplantation within the last 5 years
研究组 & 干预措施
Pembrolizumab in Participants with rrPMBCL
Participants with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) receive Pembrolizumab 200 mg by intravenous (IV) infusion on day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years).
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review
时间窗: Up to approximately 24 months
ORR is defined as the percentage of participants with response (complete response, CR or partial response, PR) according to the International Working Group (IWG) Response Assessment Criteria for Malignant Lymphoma per Cheson 2007. CR is the disappearance of all evidence of disease. PR is ≥ 50% decrease in the sum of product diameters (SPD) of the six largest dominant nodes or nodal masses, ≥ 50% decrease in SPD of splenic and hepatic nodules, no increase in the size of the other nodes, liver, or spleen plus no measurable disease in other organs and no new sites of disease. Per protocol, the percentage of participants who experienced a CR or PR as assessed by independent central review were reported.
Number of Participants Who Experienced at Least One Adverse Event (AE)
时间窗: Up to approximately 27 months
An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, which occurs during the course of the study. Per protocol, the number of participants who experienced at least one AE were reported.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
时间窗: Up to approximately 24 months
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, which occurs during the course of the study. Per protocol, the number of participants who discontinued study treatment due to an AE were reported.
次要结局
- Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator(Up to approximately 24 months)
- Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review(Up to approximately 24 months)
- Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator(Up to approximately 24 months)