AzTrials
AzTrials

Primary Mediastinal Large B-cell Lymphoma (PMBCL)Phase 2NCT05934448

Pembro Plus CAR T-cell Therapy in R/R in PMBCL

A Phase 2 study testing Pembrolizumab, Lymphodepletion Chemotherapy and Chimeric Antigen Receptor (CAR) Therapy Infusion in people with Primary Mediastinal Large B-cell Lymphoma (PMBCL) and Primary Mediastinal Large B Cell Lymphoma, run by Jennifer Crombie, MD at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This research study is evaluating the combination of drugs, pembrolizumab with chimeric antigen receptor (CAR) T-cell therapy, as a possible treatment for primary mediastinal B-cell lymphoma that has recurred after prior treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab, Lymphodepletion Chemotherapy and Chimeric Antigen Receptor (CAR) Therapy Infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
15 Nov 2023to 6 Jun 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Histologically confirmed diagnosis of PMBCL, EBV+ DLBCL or THRLBCL at one of the participating institutions.
  • Availability of archival or freshly collected tumor tissue before study enrollment. If archival tissue is unavailable or is determined to be inadequate, tumor tissue must be obtained from a biopsy performed at screening, unless an exception is given after consultation with the sponsor-investigator.
  • Eligible for standard of care CAR T-cell therapy with progression after at least two prior lines of therapy OR refractory to initial chemoimmunotherapy OR relapse within 12 months of front-line chemoimmunotherapy OR one prior line of therapy and not fit for HSCT.
  • ECOG Performance Status of 0 or 1.
  • Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO).
  • Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator), defined as follows:
Show all 17Show fewer
  • ANC ≥ 1,000/μL
  • Hemoglobin ≥ 8 g/dL
  • Platelet count ≥ 50,000/μL
  • Participants must have adequate organ as defined below:
  • Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
  • AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver involvement)
  • Adequate renal function defined by serum creatinine ≤1.5 x ULN or creatinine clearance (by Cockcroft-Gault) ≥ 40 ml/min for patients with serum creatinine >1.5 x ULN
  • At least one bi-dimensionally FDG-avid measurable lymphoma lesion on PET/CT scan, defined as ≥ 1.5 cm in its longest dimension on CT scan, or ≥ 1 cm if extranodal (and measurable).
  • Women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the informed consent form and 6 months for WOCBP and for men after the last administration of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control, e.g. intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, use of two forms of birth control, and sexual abstinence. The use of condoms by male patients is required unless the female partner is permanently sterile.
  • Age ≥18 years.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Patients in urgent need of cytoreductive therapy.
  • Participants who are receiving any other investigational agents.
  • History of other malignancies, except:
  • Malignancy treated medically or surgically with curative intent and with no known active disease present for ≥2 years before study registration
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease.
Show all 30Show fewer
  • Localized prostate cancer and low-risk prostate cancer on active surveillance
  • In the opinion of the treating investigator, there is limited potential to interfere with the safety or efficacy of the investigational regimen. Such exceptions must be approved by the Sponsor-Investigator.
  • Has received a live vaccine within 30 days prior to study registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • Less than 6 months of response to prior PD-L1 inhibitor or PD-1 inhibitor or grade 3 or higher immune-related adverse events.
  • Prior treatment with CAR T-cell therapy.
  • Lactating or pregnant. Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) at screening. WOCBP will require a negative pregnancy test within 72 hours prior to starting treatment, but eligibility for study enrollment may be confirmed based on testing at screening.
  • Known active lymphomatous involvement of the central nervous system. History of prior CNS involvement is allowed.
  • Recent infection requiring intravenous antibiotics that was completed ≤7 days before the first dose of study drug, or any uncontrolled active systemic infection.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection.
  • History of Human immunodeficiency virus (HIV)-infection.
  • Has received prior radiotherapy within 2 weeks of study registration. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Has received prior systemic anti-cancer therapy within 2 weeks or investigational agents within 4 weeks.
  • Significant liver disease, such as hepatitis (viral or non-viral) or cirrhosis
  • Prior macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH)
  • Uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of enrollment.
  • Known history of central nervous system or neurologic disease including stroke or intracranial hemorrhage within 3 months prior to enrollment or seizure disorder. Prior CNS involvement with lymphoma is allowed if previously treated with no evidence of involvement at study entry.
  • Prior solid organ or allogeneic stem cell transplant or within 6 weeks of autologous stem cell transplant.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to study registration. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Active pneumonitis or interstitial lung disease.
  • Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has not met requirements for standard of care CAR-T therapy

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Clare Phinney contact

857-215-1517

clare_phinney@dfci.harvard.edu

United States2 sites, 2 recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Clare Phinney, clare_phinney@dfci.harvard.edu

    Jennifer Crombie, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Gunjan Shah, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Trial of Pembrolizumab in Combination With Chimeric Antigen Receptor Therapy in Patients With Relapsed/Refractory Primary Mediastinal B-cell Lymphoma

This research study is evaluating the combination of drugs, pembrolizumab with chimeric antigen receptor (CAR) T-cell therapy, as a possible treatment for primary mediastinal B-cell lymphoma that has recurred after prior treatment.

The names of the study drugs involved in this study are:

  • Pembrolizumab

Standard treatment will include:

  • CAR T-cell therapy (either axicabtagene-ciloleucel or lisocabtagene maraleucel)
  • Cyclophosphamide
  • Fludarabine
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The names of the study drugs involved in this study are:

  • Pembrolizumab

Standard treatment will include:

  • CAR T-cell therapy (either axicabtagene-ciloleucel or lisocabtagene maraleucel)
  • Cyclophosphamide
  • Fludarabine Participants will receive study treatment for up to 2 years and will be followed for 5 years. It is expected that about 35 people will take part in this research study.

The U.S. Food and Drug Administration (FDA) has approved pembrolizumab for this specific disease after two or more lines of therapy, but not in combination with CAR T-cell therapy.

The CAR T-cell therapies to be used in this study are axicabtagene-ciloleucel and lisocabtagene maraleucel. The U.S. FDA has approved axicabtageneciloleucel and lisocabtagene maraleucel as treatment options for this disease, but not in combination with pembrolizumab.

A small subset of patients with T-cell histiocyte-rich large B-cell lymphoma and EBV+ large B-cell lymphoma will also be included.

Being tested
Pembrolizumab, Lymphodepletion Chemotherapy, Chimeric Antigen Receptor (CAR) Therapy Infusion, Leukapheresis
Keywords
Primary Mediastinal Large B-cell Lymphoma (PMBCL), Primary Mediastinal Large B Cell Lymphoma, Primary Mediastinal Large B-Cell Lymphoma Refractory, Primary Mediastinal Large B-Cell Lymphoma Recurrent, T-Cell/Histiocyte-Rich Large B-Cell Lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab via iv, dosage and timing per protocol

  • Lymphodepletion ChemotherapyDrug

    Also called Fludarabine, Cyclophosphamide

    Participants will undergo lymphodepleting chemotherapy (fludarabine, cyclophosphamide) for CAR T-cell therapy as per SOC

  • Chimeric Antigen Receptor (CAR) Therapy InfusionDrug

    Day 0 in the hospital and will remain in the inpatient setting for observation for a minimum of 7 days or until CAR T-cell toxicities resolve to grade 1 or better. The choice of CAR-T product will be left to the discretion of the treating investigator.

  • LeukapheresisProcedure or surgery

    manufacturing using commercial product as per standard of care (SOC) Cycle 1 Day -21 or earlier

Study groups in NCT05934448
Study groupRoleWhat they receive
PEMBROLIZUMABExperimental* Participants will undergo (leukapheresis) for manufacturing of commercial product as per standard of care (SOC) Cycle 1 Day -21or earlier * Pembrolizumab will be administered per protocol on cycle 1 day -20 and on day +1 following Chimeric Antigen Receptor (CAR) Therapy Infusion infusion, every 3 weeks for up to 2 years, unless there is confirmed progression of disease or unacceptable toxicity. * Upon the completion of successful manufacturing, patients will undergo lymphodepleting chemotherapy (fludarabine, cyclophosphamide) for chimeric antigen receptor (CAR) therapy infusion as per SOC. * Participants will receive Chimeric Antigen Receptor (CAR) Therapy Infusion (SOC) on day 0 in the hospital and will remain in the inpatient setting for observation for a minimum of 7 days or until CAR T-cell toxicities resolve to grade 1 or better. The choice of CAR-T product will be left to the discretion of the treating investigator.
Receives: Drug: Pembrolizumab; Drug: Lymphodepletion Chemotherapy; Drug: Chimeric Antigen Receptor (CAR) Therapy Infusion; Procedure: Leukapheresis

What is being measured

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

  1. Complete Response (CR) Rate at 6 Months

    Per Lugano 2014 criteria, Complete Response (CR) is defined as PET-CT, score 1, 2, or 3* with or without a residual mass on 5 point scale; or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease.

    Measured: 6 months

Secondary outcomes (9)

  1. Treatment-Related Grade 3 or Higher Cytokine Release Syndrome (CRS) Rate

    CRS rate will be summarized based on American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading (Lee et al, 2019).

    Measured: 6 months

  2. Treatment-Related Grade 3 or Higher Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Rate

    ICANS rate will be summarized based on ASTCT ICANS Consensus Grading for Adults using ICE 10-Point Neurological Assessment (Lee et al, 2019)

    Measured: 6 months

  3. Treatment-Related Grade 3 or Higher Prolonged Cytopenia Rate

    Prolonged cytopenias defined as Grade 3 or higher neutropenia, anemia, or thrombocytopenia persisting for ≥ 4 weeks from receiving CAR T-cell therapy based on CTCAEv5.

    Measured: 6 months

  4. Treatment-Related Grade 3 or Higher Immune-Related Adverse Event (irAE) Rate

    Composite rate comprised of all irAEs based on CTCAEv5

    Measured: 6 months

  5. Complete Response (CR) Rate at 6 Months in patients with EBV+ DLBCL and THRLBCL

    Per Lugano 2014 criteria, Complete Response (CR) is defined as PET-CT, score 1, 2, or 3* with or without a residual mass on 5 point scale; or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease.

    Measured: 6 months

  6. Partial Response (PR) Rate

    Per Lugano 2014 criteria, partial response (PR) is defined as PET-CT Score 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size; or On CT ≥ 50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; no increase in non-measured lesions; spleen if enlarged must have regressed by >50% in length beyond normal.

    Measured: baseline, 1 month, 3 month, and every 6 months up to 24 months

  7. Duration of Response (DOR)

    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation). CR, PR and PD are defined based on Lugano 2014 criteria.

    Measured: baseline, 1 month, 3 month, and every 6 months up to 24 months

  8. Median Progression-free survival (PFS)

    Progression-Free Survival (PFS) based on Kaplan-Meier method is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. PD is defined based on Lugano 2014 criteria.

    Measured: Baseline, 1 month, 3 month (if not CR at 1 month) and then every 6 months until 24 months.

  9. Median overall survival (OS)

    Overall Survival (OS) based on Kaplan-Meier is defined as the time from randomization (or registration) to death due to any cause or censored at date last known alive.

    Measured: Up to 5 years

Timeline

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

  1. First posted7 Jul 2023
  2. Study start15 Nov 2023
  3. Primary completion6 Jun 2027 (estimated)
  4. Study completion6 Jun 2031 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05934448
Sponsor's protocol ID
23-179
Status last verified
Mar 2026
First submitted
28 Jun 2023
Last updated
5 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab, Lymphodepletion Chemotherapy and Chimeric Antigen Receptor (CAR) Therapy Infusion in people with Primary Mediastinal Large B-cell Lymphoma (PMBCL) and Primary Mediastinal Large B Cell Lymphoma, run by Jennifer Crombie, MD at 2 sites in United States.

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 17 inclusion and 30 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: looking for participants now, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Clare Phinney (857-215-1517, clare_phinney@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) Rate at 6 Months (time frame: 6 months). 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 NCT05934448.

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 5 Mar 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in