A Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (MK-3475-A33/KEYNOTE-A33)

Lymphoma, B-Cell Clinical Trial

Official title:

A Phase 1 Clinical Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) (KEYNOTE-A33)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04317066
• Other study ID #: 3475-A33
• Secondary ID: MK-3475-A33KEYNO
• Status: Completed
• Phase: Phase 1
• Start date: June 26, 2020
• Est. completion date: April 11, 2024

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: April 11, 2024
• Est. primary completion date: April 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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 CR or 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Japan	Kyushu University Hospital ( Site 0008)	Fukuoka
Japan	Nagoya University Hospital ( Site 0002)	Nagoya	Aichi
Japan	Okayama University Hospital ( Site 0004)	Okayama
Japan	Kindai University Hospital ( Site 0001)	Osakasayama	Osaka
Japan	Hokkaido University Hospital ( Site 0006)	Sapporo	Hokkaido
Japan	National Hospital Organization Disaster Medical Center ( Site 0007)	Tachikawa	Tokyo
Japan	National Cancer Center Hospital ( Site 0005)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 0009)	Tokyo
Japan	Yamagata University Hospital ( Site 0003)	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) as Assessed by Independent Central Review	ORR is defined as the percentage of participants who have a Complete Response (CR) or Partial Response (PR). The percentage of participants who experience a CR or PR as assessed by blinded independent central review will be presented.	Up to approximately 3 years
Primary	Number of Participants Who Experienced One or More Adverse Events (AEs)	An adverse event (AE) is 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, that occurs during the course of the study.	Up to approximately 3 years
Primary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is 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, that occurs during the course of the study.	Up to approximately 2 years
Secondary	Objective Response Rate (ORR) as Assessed by Investigator	ORR is defined as the percentage of participants who have a Complete Response (CR) or Partial Response (PR). The percentage of participants who experience a CR or PR as assessed by investigator review will be presented.	Up to approximately 3 years
Secondary	Disease Control Rate (DCR) as Assessed by Independent Central Review	DCR is defined as the percentage of participants who have a Complete Response (CR), a Partial Response (PR), or stable disease (SD). The percentage of participants who experience a CR, a PR, or SD as assessed by blinded independent central review will be presented.	Up to approximately 3 years
Secondary	Disease Control Rate (DCR) as Assessed by Investigator	DCR is defined as the percentage of participants who have a Complete Response (CR), a Partial Response (PR), or stable disease (SD). The percentage of participants who experience a CR, a PR, or SD as assessed by investigator review will be presented.	Up to approximately 3 years

External Links

•   Merck Clinical Trials Information