Clinical Trials /

Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

NCT03498612

Description:

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.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases
  • Official Title: Phase II Window Study of Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

Clinical Trial IDs

  • ORG STUDY ID: 9647
  • SECONDARY ID: NCI-2018-00432
  • SECONDARY ID: 9647
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG1716072
  • NCT ID: NCT03498612

Conditions

  • B-Cell Non-Hodgkin Lymphoma
  • Follicular Lymphoma
  • Indolent Non-Hodgkin Lymphoma
  • Marginal Zone Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients 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.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Untreated indolent lymphoma including the following histologies: follicular lymphoma,
             marginal zone lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, small
             lymphocytic lymphoma, Waldenstrom's macroglobulinemia, lymphoplasmacytic lymphoma

          -  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) ≥ 1,000/mcL OR ≥ 750/mcL if neutropenia due to iBCL

          -  Platelets ≥ 75,000/mcL OR ≥ 50.000 if thrombocytopenia due to iBCL

          -  Hemoglobin ≥ 9 g/dL OR ≥ 8 g/dL if anemia due to iBCL, without transfusion or
             erythropoietin (EPO) dependency (within 7 days of assessment)

          -  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]) ≥ 60 mL/min for subject with creatinine
             levels > 1.5 X institutional ULN

          -  Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X
             ULN OR ≤ 5 X ULN for subjects with liver metastases

          -  Albumin ≥ 2.5 mg/dL

          -  International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless
             subject 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 subject 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 anti-neoplastic therapies such as 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (complete response [CR] + partial response [PR] for follicular lymphoma and marginal zone lymphoma)
Time Frame:Up to 5 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Duration of response
Time Frame:From the time by which the measurement criteria are met for CR or PR, assessed up to 5 years
Safety Issue:
Description:Kaplan Meier methodology will be used to estimate event-free curves.
Measure:Progression-free survival
Time Frame:From the first study drug administration to the first occurrence of lymphoma progression or death from any cause, assessed up to 5 years
Safety Issue:
Description: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.
Measure:Time to next therapy
Time Frame: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
Safety Issue:
Description:
Measure:Incidence of adverse events (AEs)
Time Frame:Up to 30 days after last dose
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

January 23, 2020