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

NCT05934448 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-179
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief 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. 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

Conditions

Primary Mediastinal Large B Cell Lymphoma; Primary Mediastinal Large B-Cell Lymphoma Refractory; Primary Mediastinal Large B-Cell Lymphoma Recurrent; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma; Primary Mediastinal Large B-cell Lymphoma (PMBCL)

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

Outcome Measures

Primary Outcomes (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.

  6 months

Secondary Outcomes (9)

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

  6 months

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

  6 months

• Treatment-Related Grade 3 or Higher Prolonged Cytopenia Rate

  6 months

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

  6 months

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

  6 months

Study Arms (1)

PEMBROLIZUMAB

EXPERIMENTAL

* 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.

Drug: Pembrolizumab; Drug: Lymphodepletion Chemotherapy; Drug: Chimeric Antigen Receptor (CAR) Therapy Infusion; Procedure: Leukapheresis

Interventions

Pembrolizumab DRUG

Pembrolizumab via iv, dosage and timing per protocol

Also known as: Keytruda

PEMBROLIZUMAB

Lymphodepletion Chemotherapy DRUG

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

Also known as: Fludarabine, Cyclophosphamide

PEMBROLIZUMAB

Leukapheresis PROCEDURE

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

PEMBROLIZUMAB

Chimeric Antigen Receptor (CAR) Therapy Infusion DRUG

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.

PEMBROLIZUMAB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Jennifer Crombie, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Interventions

pembrolizumab; fludarabine; Cyclophosphamide; Receptors, Chimeric Antigen; Automobiles; Leukapheresis

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear; Motor Vehicles; Transportation; Technology, Industry, and Agriculture; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Jennifer Crombie, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clare Phinney

CONTACT

857-215-1517; clare_phinney@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 7, 2023
• Study Start: November 15, 2023
• Primary Completion (Estimated): June 6, 2027
• Study Completion (Estimated): June 6, 2031
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)