Pembrolizumab in Relapsed and Refractory Gray-Zone Lymphoma (GZL), Primary Central Nervous System Lymphoma (PCNSL), and Other Extranodal Diffuse Large B-cell Lymphomas
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|ClinicalTrials.gov Identifier: NCT03255018|
Recruitment Status : Recruiting
First Posted : August 21, 2017
Last Update Posted : July 12, 2018
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.
To collect data to see if it may be effective to give pembrolizumab to people with certain types of rare, aggressive B-cell lymphomas.
People ages 14 and older who have a B-cell lymphoma, including gray-zone lymphoma or extra-nodal lymphoma
Participants will be screened with:
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.
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma Lymphoma Diffuse Large B-Cell Lymphoma Gray Zone Lymphoma Primary Central Nervious System Lymphoma||Drug: Pembrolizumab||Phase 2|
- 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 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, PD-L1 and PD-L2
- Pembrolizumab, a humanized 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
-To determine the best overall response rate of pembrolizumab in patients with relapsed and refractory GZL and extranodal DLBCL
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 14 years
- Phase 2 study of patients with relapsed and refractory GZL and extranodal DLBCL
- Patients will be treated with pembrolizumab 200 mg (flat dose) 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, PR, or 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||52 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||February 15, 2018|
|Estimated Primary Completion Date :||July 1, 2020|
|Estimated Study Completion Date :||July 1, 2022|
Subjects with gray-zone lymphoma (GZL) or extranodal DLBCL relapsed from or refractory to prior therapy with an anthracycline-based regimen
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.
- Best overall response rate of pembrolizumab in patients with relapsed/refractory gray- zone lymphomas (GZL) and extra-nodal diffuse large B-cell lymphomas (DLBCL) [ Time Frame: 24 months ]The response rate will be determined and reported along with a 95% confidence interval.
- toxicity profile of pembrolizumab in patients with GZL and extra-nodal DLBCL [ Time Frame: every 3 weeks ]The type, grade and frequency of toxicities will be reported.
- best overall response rate according to the 5-point Lugano classification for interpreting FOG-PET scans [ Time Frame: every 3-6 months for 24 months ]The response rate will be will be estimated for each of the two types of lymphoma individually using Kaplan- Meier curves with appropriate confidence intervals reported.
- duration of response for patients who respond to pembrolizumab [ Time Frame: every 3-6 months for 24 months ]The duration of response (DOR; beginning at the date clinical response is first identified) will be estimated for each of the two types of lymphoma individually using Kaplan-Meier curves with appropriate confidence intervals reported.
- progression-free survival (PFS) [ Time Frame: every 3-6 months for 24 months ]The progression free survival (PFS) will be estimated for each of the two types of lymphoma individually using Kaplan-Meier curves with appropriate confidence intervals reported.
- event-free survival (EFS) [ Time Frame: every 3-6 months for 5 years ]The event free survival (EFS) will be estimated for each of the two types of lymphoma individually using Kaplan- Meier curves with appropriate confidence intervals reported.
- overall survival (OS) [ Time Frame: every 3-6 months for 5 years ]The overall survival (OS) will be estimated for each of the two types of lymphoma individually using Kaplan- Meier curves with appropriate confidence intervals reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03255018
|Contact: Maureen E Edgerly, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Mark J Roschewski, M.D.||National Cancer Institute (NCI)|