Non-Hodgkin LymphomaPhase 2NCT03255018
Pembrolizumab in Relapsed and Refractory Gray-Zone Lymphoma (GZL), Primary Central Nervous System Lymphoma (PCNSL), and Other Extranodal Diffuse Large B-cell Lymphomas
A Phase 2 study testing Pembrolizumab in people with Non-Hodgkin Lymphoma and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Lymphoma, Diffuse Large B-Cell Lymphoma
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2018to 29 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 32Show fewer
- 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
- OR
- Direct bilirubin less than or equal to ULN for patients with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 times ULN (less than or equal to 5 X ULN if liver involvement)
- The effects of pembrolizumab on the developing human fetus are unknown. For this reason, the following measures apply:
- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first dose of pembrolizumab.
- Men and women of childbearing potential (WOCBP) who are sexually active must agree to adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 120 days after the last dose of pembrolizumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Participants must not be planning to conceive or father children within the projected duration of the trial, starting with the pre-screening/screening visit through 120 days after the last dose of pembrolizumab.
- WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.
- Ability of patient or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document
Who cannot join
- 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
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- 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
- Active graft-vs-host disease (GVHD) requiring treatment or any history of greater than or equal to grade II acute GVHD
- Seizure activity within the past 4 weeks
- Known mental or physical illness that would interfere with cooperation with the requirements of the trial or confound the results or interpretation of the results of the trial and, in the opinion of the treating investigator, would make the patient inappropriate for entry into the study.
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding must be discontinued if the mother is treated with pembrolizumab
- Received a live vaccine within 30 days of planned start of study therapy. NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab unless felt to be in the best interests of the patient in the opinion of the investigator
- Known additional malignancy that requires active systemic treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 2 Trial of Pembrolizumab in Relapsed and Refractory Gray-Zone Lymphoma (GZL), Primary Central Nervous System Lymphoma (PCNSL), and Other Extranodal Diffuse Large B-cell Lymphomas
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.
Read more
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.
Read the detailed description
Background:
- Gray-zone lymphomas (GZL) are rare, aggressive lymphomas that share clinical and biological features of diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma
- Standard upfront therapy for GZL is dose-intensive chemotherapy, though disease is often resistant; consolidative radiation therapy reserved for patients who are relapsed or refractory, and patients who fail radiation therapy have a poor prognosis
- Primary central nervous system lymphoma (PCNSL), primary testicular lymphoma (PTL), primary breast lymphoma (PBL), primary cutaneous DLBCL, leg-type, and intravascular B-cell lymphoma (IVBCL) are rare, aggressive extranodal subsets of DLBCL that usually have gene expression signatures of activated B-cell (ABC) DLBCL
- ABC-DLBCL has cure rates below 40% after standard therapy, and is associated with late recurrences, often involving the central nervous system (CNS) where treatment options are limited by chemotherapy resistance and an inability of many agents to cross the blood-brain barrier
- Molecular biology studies of GZL and extranodal DLBCL have identified potentially targetable genetic features involving the programmed death-1 (PD-1) signaling pathway
- A high proportion of GZL, PCNSL, and PTL cases have copy number alterations or chromosomal rearrangements involving the PD-1 ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2)
- Pembrolizumab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody that targets the PD-1 receptor, is a rational therapeutic target for patients with relapsed and refractory GZL, PCNSL, PTL, and other extranodal DLBCL
Objectives:
-To determine the best overall response rate of pembrolizumab in patients with relapsed and refractory GZL and extranodal DLBCL
Eligibility:
- Confirmed diagnosis of B-cell lymphoma, relapsed from or refractory to prior:
- 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 DLBCL)
- Adequate bone marrow and organ function defined
- Age greater than or equal to 18 years
Design:
- Phase 2 study of patients with relapsed and refractory GZL and extranodal DLBCL
- Patients will be treated with pembrolizumab 200 mg (flat dose) intravenous (IV) every 3 weeks provided they have clinical benefit and no unacceptable toxicity; patients who achieve a complete response (CR) will have the option stop after 1 year of therapy.
- All responding patients (CR, partial response (PR), or stable disease (SD) with clinical benefit) who subsequently relapse or progress within 1 year after discontinuation of study drug are eligible for re-treatment.
- At least 20 evaluable patients each with GZL and DLBCL will be evaluated on this protocol for the primary endpoint (overall accrual ceiling of 52 patients)
- Conditions
- Non-Hodgkin Lymphoma, Lymphoma, Diffuse Large B-Cell Lymphoma, Gray-zone Lymphoma, Primary Central Nervous System Lymphoma
- Being tested
- Pembrolizumab
- Keywords
- Monoclonal Antibody, PD-1 Receptor
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called Keytruda
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is serious. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Measured: 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
The response rate is calculated by dividing the number of participants that had a complete response (CR) or partial response (PR) to therapy measured on positron emission tomography (PET) scan in accordance with the 5-point Lugano classification. Best overall response is the best response (complete or partial response) recorded from the start of the treatment until disease progression/recurrence. The 5-Point Scale Deauville criteria scores the most intense uptake in a site of initial disease: no uptake or no residual uptake, slight uptake, but above blood pool, uptake above mediastinal but below or =to uptake in liver, uptake slightly to moderately higher than liver, \& markedly increased uptake. 5Point Scale ranges:1 to 5, 1=best; 5=worst: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 4, uptake moderately > liver; 5, uptake markedly higher than liver; X. CR=scores 1-3 on \& PR is calculated by measured change from baseline (score 4 or 5).
Measured: every 3-6 months for 24 months
Duration of Response for Participants Who Respond to Pembrolizumab
DOR is beginning at the date clinical response is first identified; measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is documented and will be estimated for each of the two types of lymphoma individually using Kaplan-Meier curves with appropriate confidence intervals reported. Response was assessed by the International Working Group response criteria (Cheson et al.). Complete response is <1 cm lymph nodes/lymph node masses, and normal bone marrow/physical exam (PE); unconfirmed complete response is >1 cm lymph nodes and >75% decrease lymph node masses, normal PE and indeterminate in bone marrow; partial response is ≥50% decrease in lymph nodes/lymph node masses, decrease in liver/spleen and irrelevant in bone marrow; and progression is >50% new or increased lymph node masses/lymph nodes, enlarging liver/spleen, and reappearance in bone marrow.
Measured: every 3-6 months for 24 months
Progression-free Survival (PFS)
PFS is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first. PFS will be estimated for each of the two types of lymphoma individually using Kaplan-Meier curves with appropriate confidence intervals reported. Response was assessed by the International Working Group response criteria (Cheson et al.). Disease relapse is decline in prognosis and progression >50% increase in lymph node masses/lymph nodes, enlarging liver/spleen, new sites and reappearance in bone marrow.
Measured: up to 2 months
Event-free Survival (EFS)
EFS is defined as the duration of time from the date of study enrollment until time of disease relapse, disease progression, alternative therapy for lymphoma given (such as radiation), or death, whichever occurs first. EFS will be estimated for each of the two types of lymphoma individually using Kaplan-Meier curves with appropriate confidence intervals reported. Response was assessed by the International Working Group response criteria (Cheson et al.). Disease relapse is decline in prognosis and progression >50% increase in lymph node masses/lymph nodes, enlarging liver/spleen, new sites and reappearance in bone marrow.
Measured: up to 2 months
Overall Survival (OS)
OS is the time from treatment start date until date of death from any cause, date last known alive or last follow up. OS will be estimated for each of the two types of lymphoma individually using Kaplan-Meier curves with appropriate confidence intervals reported.
Measured: every 3-6 months, up to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start15 Feb 2018
- Primary completion22 Oct 2022
- Study completion29 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Mark Roschewski, M.D., National Cancer Institute (NCI)
- Investigators
- Mark J Roschewski, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255018
- Sponsor's protocol ID
- 170149
- Other IDs
- 17-C-0149
- Status last verified
- Nov 2023
- First submitted
- 18 Aug 2017
- Last updated
- 28 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All large-scale genomic sequencing data will be shared with subscribers to the Database of Genotype and Phenotype (dbGaP).
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Pembrolizumab in Relapsed and Refractory Gray-Zone Lymphoma (GZL), Primary Central Nervous System Lymphoma (PCNSL), and Other Extranodal Diffuse Large B-cell Lymphomas
- ClinicalTrials.gov ID
- NCT03255018
- Acronym / sponsor ID
- 170149
- Conditions
- Non-Hodgkin Lymphoma, Lymphoma, Diffuse Large B-Cell Lymphoma, Gray-zone Lymphoma, Primary Central Nervous System Lymphoma
- Keywords
- Monoclonal Antibody, PD-1 Receptor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Feb 2018 (actual)
- Primary completion
- 22 Oct 2022 (actual)
- Study completion
- 29 Jun 2023 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Posted 28 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Gray-zone lymphomas (GZL) are rare, aggressive lymphomas that share clinical and biological features of diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma
- Standard upfront therapy for GZL is dose-intensive chemotherapy, though disease is often resistant; consolidative radiation therapy reserved for patients who are relapsed or refractory, and patients who fail radiation therapy have a poor prognosis
- Primary central nervous system lymphoma (PCNSL), primary testicular lymphoma (PTL), primary breast lymphoma (PBL), primary cutaneous DLBCL, leg-type, and intravascular B-cell lymphoma (IVBCL) are rare, aggressive extranodal subsets of DLBCL that usually have gene expression signatures of activated B-cell (ABC) DLBCL
- ABC-DLBCL has cure rates below 40% after standard therapy, and is associated with late recurrences, often involving the central nervous system (CNS) where treatment options are limited by chemotherapy resistance and an inability of many agents to cross the blood-brain barrier
- Molecular biology studies of GZL and extranodal DLBCL have identified potentially targetable genetic features involving the programmed death-1 (PD-1) signaling pathway
- A high proportion of GZL, PCNSL, and PTL cases have copy number alterations or chromosomal rearrangements involving the PD-1 ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2)
- Pembrolizumab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody that targets the PD-1 receptor, is a rational therapeutic target for patients with relapsed and refractory GZL, PCNSL, PTL, and other extranodal DLBCL
Objectives:
-To determine the best overall response rate of pembrolizumab in patients with relapsed and refractory GZL and extranodal DLBCL
Eligibility:
- Confirmed diagnosis of B-cell lymphoma, relapsed from or refractory to prior:
- 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 DLBCL)
- Adequate bone marrow and organ function defined
- Age greater than or equal to 18 years
Design:
- Phase 2 study of patients with relapsed and refractory GZL and extranodal DLBCL
- Patients will be treated with pembrolizumab 200 mg (flat dose) intravenous (IV) every 3 weeks provided they have clinical benefit and no unacceptable toxicity; patients who achieve a complete response (CR) will have the option stop after 1 year of therapy.
- All responding patients (CR, partial response (PR), or stable disease (SD) with clinical benefit) who subsequently relapse or progress within 1 year after discontinuation of study drug are eligible for re-treatment.
- At least 20 evaluable patients each with GZL and DLBCL will be evaluated on this protocol for the primary endpoint (overall accrual ceiling of 52 patients)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Gray-zone Lymphoma (GZL) or Extranodal Diffuse Large B-cell Lymphomas (DLBCL) | Experimental | Biological: PembrolizumabParticipants with gray-zone lymphoma (GZL) or extranodal DLBCL relapsed from or refractory to prior therapy with an anthracycline-based regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- 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:
- 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
Key exclusion criteria (22 listed)
- 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:
- 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:
- 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):
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaAdministered 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. | Biological | Participants with Gray-zone Lymphoma (GZL) or Extranodal Diffuse Large B-cell Lymphomas (DLBCL) |
Primary outcome
Best Overall Response Rate of Pembrolizumab in Participants With Relapsed/Refractory Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL)
Time frame: Up to 24 months
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.
6 secondary outcomes
Number of Grades 1-5 Adverse Events in Participant With Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL)
Time frame: 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
Time frame: every 3-6 months for 24 months
Duration of Response for Participants Who Respond to Pembrolizumab
Time frame: every 3-6 months for 24 months
Progression-free Survival (PFS)
Time frame: up to 2 months
Event-free Survival (EFS)
Time frame: up to 2 months
Overall Survival (OS)
Time frame: every 3-6 months, up to 2.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All large-scale genomic sequencing data will be shared with subscribers to the Database of Genotype and Phenotype (dbGaP).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark J Roschewski, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Non-Hodgkin Lymphoma and Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response Rate of Pembrolizumab in Participants With Relapsed/Refractory Gray-zone Lymphomas (GZL) and Extra-nodal Diffuse Large B-cell Lymphomas (DLBCL) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2023.