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Lymphoma, B-CellPhase 1NCT04317066

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

A Phase 1 study testing Pembrolizumab in people with Lymphoma, B-Cell, run by Merck Sharp & Dohme LLC at 9 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
9 sitesJapan
Study dates
26 Jun 2020to 11 Apr 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Japan9 sites

  • Kyushu University Hospital ( Site 0008)

    Fukuoka, 812-8582

  • Nagoya University Hospital ( Site 0002)

    Nagoya, Aichi-ken, 466-8560

  • Okayama University Hospital ( Site 0004)

    Okayama, 700-8558

  • Hokkaido University Hospital ( Site 0006)

    Sapporo, Hokkaido, 060-8648

  • Kindai University Hospital ( Site 0001)

    Sayama, Osaka, 589-8511

  • National Hospital Organization Disaster Medical Center ( Site 0007)

    Tachikawa, Tokyo, 190-0014

  • National Cancer Center Hospital ( Site 0005)

    Tokyo, 104-0045

  • Tokyo Metropolitan Komagome Hospital ( Site 0009)

    Tokyo, 113-8677

  • Yamagata University Hospital ( Site 0003)

    Yamagata, 990-9585

Other trials in Japan

About this study

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)

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.

Being tested
Pembrolizumab
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Medical subject headings
Lymphoma, B-Cell, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called KEYTRUDA®, MK-3475

    Pembrolizumab 200 mg by intravenous (IV) infusion, given on day 1 of each 3-week cycle.

Study groups in NCT04317066
Study groupRoleWhat they receive
Pembrolizumab in Participants with rrPMBCLExperimentalParticipants 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).
Receives: Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review

    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.

    Measured: Up to approximately 24 months

  2. Number of Participants Who Experienced at Least One Adverse Event (AE)

    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.

    Measured: Up to approximately 27 months

  3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

    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.

    Measured: Up to approximately 24 months

Secondary outcomes (3)

  1. Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator

    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.

    Measured: Up to approximately 24 months

  2. Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review

    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.

    Measured: Up to approximately 24 months

  3. Disease Control Rate (DCR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Investigator

    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.

    Measured: Up to approximately 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2020
  2. Study start26 Jun 2020
  3. Primary completion11 Apr 2024
  4. Study completion11 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04317066
Sponsor's protocol ID
3475-A33
Other IDs
MK-3475-A33, KEYNOTE-A33, 205262, 2080225167
Status last verified
Mar 2025
First submitted
19 Mar 2020
Last updated
6 Apr 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Kato K, Nakamura S, Wakana A, Koh Y, Izutsu K. Pembrolizumab in Japanese patients with primary mediastinal large B-cell lymphoma: results from the KEYNOTE-A33 study. Int J Clin Oncol. 2024 Dec;29(12):1977-1983. doi: 10.1007/s10147-024-02627-8. Epub 2024 Sep 18.

    PubMed 39294486

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab in people with Lymphoma, B-Cell, run by Merck Sharp & Dohme LLC at 9 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) Using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma as Assessed by Independent Central Review (time frame: Up to approximately 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04317066, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.

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