A Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (MK-3475-A33/KEYNOTE-A33)
- Registration Number
- NCT04317066
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pembrolizumab in Participants with rrPMBCL Pembrolizumab 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).
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review 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) 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) 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.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator 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 investigator review were reported.
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 The DCR was defined as the percentage of participants in the analysis population who have achieved a CR, PR or stable disease (SD) response prior to PD 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 and PR is the regression of measurable disease and no new sites of disease. SD is the failure to attain CR/PR or PD. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Per protocol, the percentage of participants who experienced a CR, a PR, or SD as assessed by independent central review were reported.
Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator Up to approximately 24 months The DCR was defined as the percentage of participants in the analysis population who have achieved a CR, PR or stable disease (SD) response prior to PD 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 and PR is the regression of measurable disease and no new sites of disease. SD is the failure to attain CR/PR or PD. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Per protocol, the percentage of participants who experienced a CR, a PR, or SD as assessed by investigator review were reported.
Trial Locations
- Locations (9)
Okayama University Hospital ( Site 0004)
🇯🇵Okayama, Japan
Kindai University Hospital ( Site 0001)
🇯🇵Osakasayama, Osaka, Japan
National Hospital Organization Disaster Medical Center ( Site 0007)
🇯🇵Tachikawa, Tokyo, Japan
Tokyo Metropolitan Komagome Hospital ( Site 0009)
🇯🇵Tokyo, Japan
Kyushu University Hospital ( Site 0008)
🇯🇵Fukuoka, Japan
Hokkaido University Hospital ( Site 0006)
🇯🇵Sapporo, Hokkaido, Japan
Nagoya University Hospital ( Site 0002)
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital ( Site 0005)
🇯🇵Tokyo, Japan
Yamagata University Hospital ( Site 0003)
🇯🇵Yamagata, Japan