Phase 2 N=12 Treatment

Pembrolizumab in Relapsed and Refractory Gray-Zone Lymphoma (GZL), Primary Central Nervous System Lymphoma (PCNSL), and Other Extranodal Diffuse Large B-cell Lymphomas

Non-Hodgkin Lymphoma · Lymphoma · Diffuse Large B-Cell Lymphoma · Gray-zone Lymphoma · Primary Central Nervous System Lymphoma

Bottom Line

View on ClinicalTrials.gov: NCT03255018 ↗

Enrolled (actual)

Serious AEs

45.5%

Results posted

Nov 2023

Primary outcome: Primary: Best Overall Response Rate of Pembrolizumab in Participants With Relapsed/Refractory Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL) — 50; 0; 0; 0 percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Pembrolizumab (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Oct 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Best Overall Response Rate of Pembrolizumab in Participants With Relapsed/Refractory Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL)	50; 0; 0; 0; 0; 11	—
SECONDARY Number of Grades 1-5 Adverse Events in Participant With Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL)	5; 35; 0; 20; 0; 8	—
SECONDARY Best Overall Response Rate According to the 5-point Lugano Classification for Interpreting 18 F-fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) Scans	100; 0; 0; 0; 0; 0	—
SECONDARY Duration of Response for Participants Who Respond to Pembrolizumab	18.25; 0.9	—
SECONDARY Progression-free Survival (PFS)	NA; 1.4	—
SECONDARY Event-free Survival (EFS)	NA; 1.4	—
SECONDARY Overall Survival (OS)	NA; 28.8	—

Summary

Background: B-cell lymphoma is a cancer of white blood cells that are found in lymph nodes. Some kinds of these cancers, such as gray-zone and extra-nodal, are rare and often aggressive. They are usually resistant to current treatments. Researchers want to see if a drug called pembrolizumab may treat these types of lymphoma. Objective: To collect data to see if it may be effective to give pembrolizumab to people with certain types of rare, aggressive B-cell lymphomas. Eligibility: People ages 18 and older who have a B-cell lymphoma, including gray-zone lymphoma or extra-nodal lymphoma Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Scans. They will lie in a machine that takes images. A tissue sample from a previous procedure will be tested. The study will be done in 21-day cycles. During the study, participants: Will repeat the screening tests. Will get the study drug as an infusion into a vein over about 30 minutes. Will have a cheek swab and/or saliva sample collected. May have a bone marrow aspiration. A needle will be put into the hipbone, and a small amount of bone marrow will be taken out. May have a lumbar puncture. If cerebrospinal fluid is collected, researchers will study it. May have an eye exam. May provide tissue samples. May have tumor samples taken. Participants will have a visit about 30 days after the last dose of the study drug. They will then have 4 visits in year 1, 2 visits a year in years 2-5, and once each year thereafter. They will also be contacted by phone.

Eligibility Criteria

INCLUSION CRITERIA:
Patients must have a diagnosis of B-cell lymphoma confirmed by Laboratory of Pathology, National Cancer Institute (NCI), that is relapsed from or refractory to prior therapy as follows:
Cohort 1: B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (i.e., Gray-zone lymphoma or GZL)
Cohort 2: Extranodal diffuse large B-cell lymphoma involving one or more of the specified extranodal sites (i.e., extranodal diffuse large B-cell lymphoma (DLBCL). The following subtypes are included (they do not have to be confirmed as non-germinal center (non-GCB) subtype for study entry):
Primary central nervous system (CNS) lymphoma (PCNSL)
Primary testicular lymphoma (PTL)
Primary breast lymphoma (PBL)
Primary cutaneous DLBCL, leg-type
Intravascular large B-cell lymphoma (IVBCL)
Diffuse large B-cell, not otherwise specified (NOS), activated B-cell type, involving 1 or more extranodal site

NOTE: For GZL, diagnosis will be in accordance with the 2016 World Health Organization classification of lymphoid malignancies. Patients diagnosed with other extranodal DLBCL subtypes or that are not otherwise specified (NOS) must involve at least 1 extranodal site and must be considered non-GCB by local immunohistochemistry algorithms. Cases that are non-GCB by the Hans criteria are considered eligible as well as cases of DLBCL that are both cluster of differentiation 10 positive (CD10+) and multiple myeloma 1 positive (MUM1+).

Evaluable disease by clinical exam (i.e., palpable lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., lymphoma involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry), and/or imaging (measurable lymph nodes or masses on computed tomography (CT) or magnetic resonance imaging (MRI) and/or evaluable fluorine-18-deoxyglucose (FDG)-avid lesions on positron emission tomography (PET)
Adequate tumor tissue (archival or fresh) must be available for correlative studies. NOTE: Tumor tissue may be from any previously collected tissue and adequacy is at the discretion of the Principal Investigator. If prior tissue is not available, patient must be willing to undergo baseline tumor biopsy.
Be 18 years of age or older on day of signing informed consent
Adequate performance status (PS) as follows:
Patients greater than or equal to 18 years must have Eastern Cooperative Oncology Group (ECOG) 0-1 (and Karnofsky greater than or equal to 60%)

NOTE: Patients greater than or equal to 18 years with an ECOG PS of 2 and Karnofsky greater than or equal to 60 will be considered eligible at the discretion of the Principal Investigator if decreased ECOG performance status is felt to be related to residual neurologic deficits caused by CNS disease involvement that are not progressive or anticipated to cause clinical management problems during study participation.

Adequate organ function as evidenced by the following laboratory parameters (unless related to lymphoma infiltration at the discretion of the investigator):
Absolute neutrophil count (ANC) greater than or equal to 750 /mcL
Platelets greater than or equal to 50,000/mcL (transfusions not permitted)
Hemoglobin greater than or equal to 9 g/dL (transfusions permitted)
Serum creatinine: Adults: less than or equal to 1.5 times upper limit of normal (ULN). Children: age greater than or equal to 14: less than or equal to 1.5 mg/dL OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl):

Greater than or equal to 30 mL/min/1.73 m(2) for subject with creatinine levels > 1.5 times institutional ULN (CrCl should be calculated per institutional standard)

--Serum total bilirubin less than or equal to 1.5 times ULN

Direct bilirubin less than or equal to ULN for patients with total bilirubin levels > 1.5 ULN

Aspartate

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Data sourced from ClinicalTrials.gov (NCT03255018). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.