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

NCT06242834 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 23H05NCI-2024-00285STU00220351P30CA060553
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Event free survival

  Event is defined as any of the following (whichever occurs first): death from any cause, progressive disease, failure to achieve complete or partial response by 6 months in CAR T patients, or start of new antineoplastic therapy due to efficacy concerns. Analysis will be performed using one sample exact test for proportions, comparing the 6-month EFS rate to the 45% historic control rate.

  At 6 months

Secondary Outcomes (6)

• Progression free survival

  From autologous stem cell transplantation (ASCT) or chimeric antigen receptor (CAR) T-cell infusion until radiologically documented disease progression or death from any cause, whichever occurs first, up to 3 years

• Overall survival

  From ASCT or CAR T-cell infusion until death from any cause, up to 3 years

• Incidence of adverse events

  From the start of CAR T or ASCT up to 30 days after treatment discontinuation

• Objective response rate (ORR)

  At month 3, 6, 12, and 18

• Complete response rate

  At month 3, 6, 12, and 18

Study Arms (1)

Treatment (pembrolizumab, tazemetostat)

EXPERIMENTAL

Starting on day 14 after standard of care ASCT or CAR-T cell treatment patients receive pembrolizumab IV on day 1 of each cycle. Starting cycle 2, patients receive tazemetostat PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening, CT scan, PET scan, and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Drug: Tazemetostat

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (pembrolizumab, tazemetostat)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (pembrolizumab, tazemetostat)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (pembrolizumab, tazemetostat)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, Keytruda, Lambrolizumab, MK-3475, Pembrolizumab Biosimilar BCD-201, SCH 900475

Treatment (pembrolizumab, tazemetostat)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (pembrolizumab, tazemetostat)

Tazemetostat DRUG

Given PO

Also known as: E7438, EPZ-6438, EPZ6438

Treatment (pembrolizumab, tazemetostat)

Eligibility Criteria

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

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)

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:

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Specimen Handling; pembrolizumab; Magnetic Resonance Spectroscopy; tazemetostat

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Reem Karmali, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 29, 2024
• First Posted: February 5, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): April 24, 2027
• Study Completion (Estimated): November 24, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (2)