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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Pembrolizumab via iv, dosage and timing per protocol
Participants will undergo lymphodepleting chemotherapy (fludarabine, cyclophosphamide) for CAR T-cell therapy as per SOC
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.
manufacturing using commercial product as per standard of care (SOC) Cycle 1 Day -21 or earlier
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGComplete 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.
Time frame: 6 months
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).
Time frame: 6 months
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)
Time frame: 6 months
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.
Time frame: 6 months
Treatment-Related Grade 3 or Higher Immune-Related Adverse Event (irAE) Rate
Composite rate comprised of all irAEs based on CTCAEv5
Time frame: 6 months
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.
Time frame: 6 months
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.
Time frame: baseline, 1 month, 3 month, and every 6 months up to 24 months
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.
Time frame: baseline, 1 month, 3 month, and every 6 months up to 24 months
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.
Time frame: Baseline, 1 month, 3 month (if not CR at 1 month) and then every 6 months until 24 months.
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.
Time frame: Up to 5 years
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