Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

Phase II Window Study of Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

This phase II trial studies how well pembrolizumab works in treating patients with B-cell non-Hodgkin lymphoproliferative diseases that have not been treated. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Study Overview

• Status: Active, not recruiting
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma; Indolent B-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Detailed Description

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then up to 5 years.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be willing and able to provide written informed consent/assent for the trial

• Must have measurable disease defined by at least one of the following criteria:

  * Lesions greater than 1.5 cm that can be accurately measured in two dimensions by computed tomography (CT) (preferred), or magnetic resonance imaging (MRI)

• Must have indication for treatment (adapted from National Comprehensive Cancer Network [NCCN] 2015 guidelines)

  * Any of the following constitute an indication for treatment:

  • Significant symptoms due to any iBCL: Which may include pain/discomfort, limitation of function, fatigue/malaise/constitutional symptoms, B-symptoms (fever, weight loss, night sweats), pruritus
  • Threatened end-organ function due to any iBCL
  • Progressive cytopenia secondary to any iBCL
  • Steady progression of follicular lymphoma (FL) and marginal zone lymphoma (MZL)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 500/uL Note: Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. No lower limit if cytopenia is related to bone marrow involvement.
• Platelets >= 25000/uL Note: Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. No lower limit if cytopenia is related to bone marrow involvement.
• Hemoglobin >= 8 g/dL Note: Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed. No lower limit if cytopenia is related to bone marrow involvement.

• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (GFR can also be used in place of creatinine or CrCl)

  * Creatinine clearance should be calculated per institutional standard

• Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN ( =< 5 x ULN for participants with liver metastases)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had prior chemotherapy, radiation therapy, or immunotherapy for the diagnosis of iBCL
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has 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); 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
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Be in urgent need of therapy for lymphoma related complications (such as hyperviscosity syndrome) and those with bulky disease

• Has 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (pembrolizumab); Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 18 cycles in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (Complete Response [CR] + Partial Response [PR] for Follicular Lymphoma and Marginal Zone Lymphoma)	Measured by Lugano Criteria evaluated by positron emission tomography (PET)/computed tomography (CT) or CT or white blood cell count for chronic lymphocytic leukemia (CLL). The corresponding 95% two-sided confidence interval will be derived.	Up to 8 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	Kaplan Meier methodology will be used to estimate event-free curves.	From the time by which the measurement criteria are met for CR or PR, whichever is recorded first, until death or the first date by which recurrent or progressive disease is objectively documented, assessed up to 5 years
Progression-free Survival	Data for subjects without disease progression or death will be censored at the date of the last tumor assessment. Kaplan-Meier methodology will be used to estimate the event-free curves.	From the first study drug administration to the first occurrence of lymphoma progression or death from any cause, assessed up to 5 years
Time to Next Therapy		From the time of first study drug administration until the date of the first subsequent therapy given to treat the indolent B-cell non-Hodgkin lymphoproliferative diseases, assessed up to 5 years
Count of Participants Who Experience Adverse Events (AEs)	Safety summaries will include tabulations in the form of tables. The frequency of treatment-emergent AE's will be summarized. Additional AE summaries will include AE frequency by AE severity and relationship to the study drug.	Up to 90 days after last dose, up to 1 year.

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Ajay K. Gopal, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2018
• Primary Completion (Actual): June 9, 2021
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: April 6, 2018
• First Posted (Actual): April 13, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Lymphoproliferative Disorders; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 9647 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2018-00432 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RG1716072 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No