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

NCT03255018 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17014917-C-0149
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Monoclonal Antibody; PD-1 Receptor

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate of Pembrolizumab in Participants With Relapsed/Refractory Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL)

  Response was assessed by the International Working Group (IWG) response criteria which utilizes computed tomography (CT) scan to measure lymph node masses to assess response, bone marrow biopsies and aspirates done only if positive at the time of diagnosis or if clinically indicated. Response is calculated by measuring the sum of the products of all target lesions and then calculating the percent change from baseline or nadir. Products are calculated by multiplying the longest length by the perpendicular width of each target lesion. Confirmed complete response is \<1 cm lymph nodes/lymph node masses; unconfirmed complete response is \>1 cm lymph nodes and \>75% decrease in size of lymph node masses; partial response is ≥50% decrease in size of lymph nodes/lymph node masses; and progression is \>50% new or increased lymph node masses/lymph nodes. Complete response (confirmed) followed by complete response(unconfirmed) and partial response are associated with better outcomes in that order.

  Up to 24 months

Secondary Outcomes (6)

• Number of Grades 1-5 Adverse Events in Participant With Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL)

  Adverse events are collected from the first dose of therapy through 30 days past the last dose of study drug or start of new anti-cancer therapy, approximately 5 months and 7 days for cohort 1, and 44 months and 25 days for cohort 2.

• Best Overall Response Rate According to the 5-point Lugano Classification for Interpreting 18 F-fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) Scans

  every 3-6 months for 24 months

• Duration of Response for Participants Who Respond to Pembrolizumab

  every 3-6 months for 24 months

• Progression-free Survival (PFS)

  up to 2 months

• Event-free Survival (EFS)

  up to 2 months

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

  Adverse events are collected from the first dose of therapy through 30 days past the last dose of study drug or start of new anti-cancer therapy., approximately 5 months and 7 days for cohort 1, and 44 months and 25 days for cohort 2.

Study Arms (1)

Participants with Gray-zone Lymphoma (GZL) or Extranodal Diffuse Large B-cell Lymphomas (DLBCL)

EXPERIMENTAL

Participants with gray-zone lymphoma (GZL) or extranodal DLBCL relapsed from or refractory to prior therapy with an anthracycline-based regimen

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Administered intravenously (IV) at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity; treatment may continue indefinitely if clinical benefit with options for treatment interruption if responding disease and re-treatment upon relapse.

Also known as: Keytruda

Participants with Gray-zone Lymphoma (GZL) or Extranodal Diffuse Large B-cell Lymphomas (DLBCL)

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 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%)

You may not qualify if:

• Patients with DLBCL who best fit the criteria of Epstein-Barr virus (EBV)+ DLBCL, NOS are not eligible
• Current or prior anti-cancer treatment prior to the first dose of pembrolizumab as defined below:
• Chemotherapy, targeted small molecule therapy, or other anti-cancer treatment not otherwise specified below within 2 weeks
• Radiation therapy within 2 weeks
• Anti-cancer monoclonal antibody (mAb) treatment within 4 weeks
• Use of an investigational agent (e.g., biologic, drug, or other) within 4 weeks
• Allogeneic stem cell transplant within 100 days
• Prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed death ligand 2 (PD-L2) agent at any time
• No current use of systemic corticosteroids at physiologic doses \> 10 mg/day of dexamethasone or equivalent are permitted. Patients receiving current systemic steroids must be on a stable steroid dose (i.e., less than or equal to 10 mg/day of dexamethasone or equivalent at the same dose for at least 7 days). Patients who recently discontinued systemic steroids must have completed them at least 7 days prior to entry.
• Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator:
• 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.
• History of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis; as well as active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV):
• Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV deoxyribonucleic acid (DNA) is undetectable.
• Uncontrolled and/or symptomatic thyroid disease

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Mark J. Roschewski
• Organization: National Cancer Institute

mark.roschewski@nih.gov

240-760-6183

Study Officials

• Mark J Roschewski, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: August 21, 2017
• Study Start: February 15, 2018
• Primary Completion: October 22, 2022
• Study Completion: June 29, 2023
• Last Updated: November 28, 2023
• Results First Posted: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the Database of Genotype and Phenotype (dbGaP) through requests to the data custodians.

Locations

US (1)