Pembrolizumab and Tazemetostat to Overcome Immune Tolerance Following ASCT or CAR T-cell Therapy in Patients With Aggressive B-Cell Non-Hodgkin's Lymphoma

Running, not enrolling · Phase 2

Conditions studied: B-Cell Non-Hodgkin Lymphoma

In brief

This phase II trial tests how well pembrolizumab and tazemetostat work to treat patients who have received autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T cell therapy for aggressive non hodgkins lymphoma. A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tazemetostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and tazemetostat may work better to treat patients who have received ASCT or CAR-T cell therapy for aggressive non hodgkins lymphoma.

Key facts

Study ID

NCT06242834

Run by

Northwestern University

People needed

32

Starts

2024-09-30

Expected to finish

2028-11-24

Last updated by the study team

2026-07-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have a histo-pathologically confirmed aggressive B-cell NHL intended for or currently undergoing standard of care ASCT or CAR T-cell therapy.
• Note: Patients should have met the Food and Drug Administration (FDA) approved indications for the respective CAR T cell construct being used. Standard of care/FDA approved CAR-Ts for this population include axicabtagene ciloleucel, tisagenlecleucel or lisocabtagene maraleucel, any of which may have been used for this patients and is provider dependent. Out of specification products of these respective CAR Ts may also be utilized if intended for FDA approved indication by way of expanded access if the provider feels that the product offers similar efficacy and safety as compared to commercial product per guidance provided by manufacturer. For the purpose of this study, aggressive B-cell NHL histologies should conform to the label indications for the respective CAR-T being utilized. Accordingly, CAR-T eligible histologies include the following groups according to the 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
• High-grade B-cell lymphoma, Not Otherwise Specified (NOS)
• Diffuse large B-cell lymphoma (DLBCL), NOS
• Diffuse large B-cell lymphoma (DLBCL), NOS; Germinal center B-cell type** [Refer note below]
• Diffuse large B-cell lymphoma (DLBCL), NOS; Non-germinal center B cell type** [Refer note below]
• Large B-cell lymphoma with IRF4 rearrangement (subtype of DLCBL)
• T-cell/histiocyte-rich large B-cell lymphoma (subtype of DLCBL)
• Primary cutaneous DLBCL, leg type (subtype of DLCBL)
• Epstein Barr Virus (EBV)+ DLBCL, NOS (subtype of DLCBL)
• DLBCL associated with chronic inflammation (subtype of DLCBL)
• Primary mediastinal (thymic) large B-cell lymphoma
• Intravascular large B-cell lymphoma (subtype of DLCBL)
• Transformed indolent B-cell lymphoma; composite lymphomas with aggressive B-cell NHL as outlined above and indolent lymphomas are also allowable if felt to represent transformation.
• NOTE: * Cell of origin will be determined by Hans criteria (immuno histochemistry). We have therefore updated criteria to indicate non-germinal center B-cell type to reflect this (rather than activated B-cell [ABC] subtype which implies use of molecular testing)
• For CAR T-cell therapy, patients must have metabolically active disease on PET/CT prior to therapy; For ASCT therapy, patients must be in complete remission
• Patients must be age ≥ 18 years on the day of signing informed consent
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients must have a life expectancy of greater than 12 weeks
• Absolute neutrophil count (ANC)* ≥ 500/μL neutrophil count prior to either admission for ASCT or CAR T-cell apheresis Note: * Use of growth factor is allowable if deemed clinically appropriate by the treating physician up to the day prior to LDC/conditioning chemotherapy (i.e. if felt to be disease related) Patients must meet the parameter at screening if intended for ASCT or CAR-T treatment but have not yet received the cellular therapeutic. For patients enrolled after receiving ASCT or CAR T-cell therapy, patients will be eligible if they meet the criteria on day 1 of either conditioning chemotherapy (ASCT) or lymphodepleting chemotherapy (LDC) (CAR-T)
• Platelets (PLT) ≥ 50,000/μL within 14 days prior to either admission for ASCT or CAR T-cell apheresis, unless deemed to be related to disease (transfusion not permitted within 7 days) Minimum platelet count requirement in those with bone marrow involvement will be ≥ 25,000 Patients must meet the parameter at screening if intended for ASCT or CAR-T treatment but have not yet received the cellular therapeutic. For patients enrolled after receiving ASCT or CAR T-cell therapy, patients will be eligible if they meet the criteria on day 1 of either conditioning chemotherapy (ASCT) or lymphodepleting chemotherapy (LDC) (CAR-T)
• Total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL), OR direct bilirubin ≤ ULN for patients with total bilirubin > 1.5 x ULN Patients must meet the parameter at screening if intended for ASCT or CAR-T treatment but have not yet received the cellular therapeutic. For patients enrolled after receiving ASCT or CAR T-cell therapy, patients will be eligible if they meet the criteria on day 1 of either conditioning chemotherapy (ASCT) or lymphodepleting chemotherapy (LDC) (CAR-T)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 x institutional ULN Patients must meet the parameter at screening if intended for ASCT or CAR-T treatment but have not yet received the cellular therapeutic. For patients enrolled after receiving ASCT or CAR T-cell therapy, patients will be eligible if they meet the criteria on day 1 of either conditioning chemotherapy (ASCT) or lymphodepleting chemotherapy (LDC) (CAR-T)
• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x institutional ULN Patients must meet the parameter at screening if intended for ASCT or CAR-T treatment but have not yet received the cellular therapeutic. For patients enrolled after receiving ASCT or CAR T-cell therapy, patients will be eligible if they meet the criteria on day 1 of either conditioning chemotherapy (ASCT) or lymphodepleting chemotherapy (LDC) (CAR-T)
• Creatinine clearance ≥ 30 mL/min estimated by the Cockcroft-Gault equation Patients must meet the parameter at screening if intended for ASCT or CAR-T treatment but have not yet received the cellular therapeutic. For patients enrolled after receiving ASCT or CAR T-cell therapy, patients will be eligible if they meet the criteria on day 1 of either conditioning chemotherapy (ASCT) or lymphodepleting chemotherapy (LDC) (CAR-T)

You may not qualify if…

• Patients who are currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study intervention Exception: Out of spec CAR-T products are permitted
• Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) or prior exposure to EZH2 inhibitors
• Patients who have received prior radiotherapy within 14 days of start of study intervention
• Note: Patients must have recovered from all radiation-related toxicities, not require corticosteroids; patients with radiation pneumonitis are excluded
• Note: A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
• Patients who have had major surgery within 4 weeks before the first planned dose of tazemetostat (i.e. cycle 2, day 1)
• Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to the first planned dose of tazemetostat
• Patients with a known history of Human Immunodeficiency Virus (HIV) infection
• Patients with a known history of chronic hepatitis B (HBV) infection
• Note: Patients who are hepatitis B surface antigen (HBsAg) positive, have received antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to registration are eligible. Patients should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention
• Patients with any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN)
• Patients with any prior history of T-cell lymphoblastic lymphoma (T-LBL)/ T cell acute lymphoblastic leukemia (T-ALL) or B cell acute lymphoblastic leukemia (B-ALL)
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or tazemetostat
• Patients receiving medications or substances that are inhibitors or inducers of CYP450 enzymes are eligible as long as they meet the criteria
• Patients with a diagnosis of immunodeficiency or patients receiving chronic systemic glucocorticoids (in dosing exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study drug. Exceptions are:
• To modulate symptoms of an adverse events (AE) that is suspected to have an immunologic etiology or related to prior CAR T-cell therapy
• For the prevention of emesis
• To premedicate for IV contrast allergies
• To treat chronic obstructive pulmonary disease (COPD) exacerbations (only short-term oral or IV use in doses >10 mg/day prednisone equivalent)
• For topical use or ocular use
• Intraarticular joint use
• For inhalation in the management of asthma or chronic obstructive pulmonary disease
• Patients who have 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)
• Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• Patients who have received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention

Where it is running

• Northwestern University — Chicago, Illinois, United States
• University of Iowa — Iowa City, Iowa, United States

Full record on ClinicalTrials.gov

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