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Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases

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ClinicalTrials.gov Identifier: NCT03498612
Recruitment Status : Not yet recruiting
First Posted : April 13, 2018
Last Update Posted : April 13, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Brief Summary:
This phase II trial studies how well pembrolizumab works in treating participants with B-cell non-Hodgkin lymphoproliferative diseases that have not been treated. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of cancer cells to grow and spread.

Condition or disease Intervention/treatment Phase
B-Cell Non-Hodgkin Lymphoma Waldenstrom Macroglobulinemia Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Lymphoplasmacytic Lymphoma Follicular Lymphoma Indolent Non-Hodgkin Lymphoma Marginal Zone Lymphoma Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To gain a preliminary assessment of the efficacy of pembrolizumab as monotherapy for patients with untreated indolent B-cell non-Hodgkin lymphoproliferative diseases (iBCL) based on overall response rate (ORR) measured at the end of a 6-cycle treatment period.

SECONDARY OBJECTIVES:

I. To assess the safety and toxicity profile of pembrolizumab in patients with untreated iBCL.

II. To measure the efficacy of pembrolizumab used as monotherapy for patients with untreated iBCL by assessing clinical outcomes including complete response rate (CR), time to next therapy (TNT), progression-free survival (PFS), and the duration of response (DOR).

OUTLINE:

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

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Window Study of Pembrolizumab in Untreated B-Cell Non-Hodgkin Lymphoproliferative Diseases
Estimated Study Start Date : May 16, 2018
Estimated Primary Completion Date : March 14, 2020
Estimated Study Completion Date : March 14, 2022


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



Primary Outcome Measures :
  1. Overall response rate (complete response [CR] + partial response [PR] for follicular lymphoma and marginal zone lymphoma) [ Time Frame: Up to 5 years ]
    Measured by Lugano Criteria evaluated by PET/CT or CT or white blood cell count for CLL. The corresponding 95% two-sided confidence interval will be derived.


Secondary Outcome Measures :
  1. Duration of response [ Time Frame: From the time by which the measurement criteria are met for CR or PR, assessed up to 5 years ]
    Kaplan Meier methodology will be used to estimate event-free curves.

  2. 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 ]
    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.

  3. 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 ]
  4. Incidence of adverse events (AEs) [ Time Frame: Up to 30 days after last dose ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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): NCT03498612


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal         
Principal Investigator: Ajay K. Gopal         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03498612     History of Changes
Other Study ID Numbers: 9647
NCI-2018-00432 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9647 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: April 13, 2018    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell, Marginal Zone
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Pembrolizumab
Antineoplastic Agents