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

• Status: Not yet recruiting
• Trial end date: 0000-00-00
• Target enrollment: 52
• Participant gender: All

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 14 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Pembrolizumab
• Last Updated: 2017-08-19

Criteria

• INCLUSION CRITERIA:

• Patients must have a confirmed diagnosis of GZL or an extra-nodal DLBCL confirmed by Laboratory of Pathology, NCI

• Cohort 1: Gray-zone lymphoma relapsed from or refractory to prior therapy with an anthracycline-based regimen

• Cohort 2: Extra-nodal diffuse large B-cell lymphomas relapsed from or refractory to prior therapy with an anthracycline-based regimen; the following subtypes are included (they do not have to be confirmed as ABC subtype for study entry)

Primary CNS lymphoma (PCNSL)

Primary testicular lymphoma (PTL)

Primary breast lymphoma (PBL)

Primary cutaneous DLBCL, leg-type

Intravascular B-cell lymphoma (IVBCL)

• 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 CT or MRI and/or evaluable FDG-avid lesions on PET)

• Adequate tumor tissue (archival or fresh) must be available for correlative studies.

• Be 14 years of age or older on day of signing informed consent

• Adequate performance status as follows:

• Patients greater than or equal to 16 years must have ECOG Performance Status 0-2 (Karnofsky greater than or equal to 60%)

• Pediatric patients < 16 years must have Lansky play-performance of 60-100%

• Adequate organ function as evidenced by the following laboratory parameters:

• 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 (GFR can also be used in place of creatinine or CrCl):

Greater than or equal to 40 mL/min/1.73 m(2) for subject with creatinine levels > 1.5 times institutional ULN

--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

• AST (SGOT) and ALT (SGPT) less than or equal to 3 times ULN

• 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

EXCLUSION CRITERIA:

• 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-PD-1, anti-PD-L1, or anti-PD-L2 agent at any time

• 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.

• Hepatitis B virus surface antigen or Hepatitis B core antibody positive

• Active hepatitis C infection. NOTE: Subjects who are hepatitis C antibody positive will need to have a negative PCR result before enrollment. Those with a positive PCR for hepatitis C are excluded.

• Uncontrolled and/or symptomatic thyroid disease

• Active graft-vs-host disease (GVHD) requiring treatment or any history of >= grade II acute GVHD

• Seizure activity within the past 4 weeks

• Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab

• 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