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
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.
Patients in urgent need of cytoreductive therapy.
Participants who are receiving any other investigational agents.
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
Single group
Pembrolizumab
DrugPembrolizumab via iv, dosage and timing per protocol
Lymphodepletion Chemotherapy
DrugParticipants will undergo lymphodepleting chemotherapy (fludarabine, cyclophosphamide) for CAR T-cell therapy as per SOC
Chimeric Antigen Receptor (CAR) Therapy Infusion
DrugDay 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.
Leukapheresis
Procedure/Surgerymanufacturing using commercial product as per standard of care (SOC) Cycle 1 Day -21 or earlier
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.
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).
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)
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.
Treatment-Related Grade 3 or Higher Immune-Related Adverse Event (irAE) Rate
Composite rate comprised of all irAEs based on CTCAEv5
Click on the lead sponsor to view all of their trials.
Jennifer Crombie, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Merck Sharp & Dohme LLC
Collaborator
