Clinical Trials /

Rituximab and Pembrolizumab in Treating Patients With Relapsed or Refractory Follicular Lymphoma or Diffuse Large B Cell Lymphoma

NCT03401853

Description:

This phase II trial studies how well rituximab and pembrolizumab work in treating patients with follicular lymphoma or diffuse large B cell lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Rituximab and Pembrolizumab in Treating Patients With Relapsed or Refractory Follicular Lymphoma or Diffuse Large B Cell Lymphoma
  • Official Title: Phase II Study of Rituximab Plus Pembrolizumab (MK-3475) in Subjects With Relapsed Follicular and Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 9469
  • SECONDARY ID: NCI-2017-02361
  • SECONDARY ID: 9469
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03401853

Conditions

  • Recurrent Diffuse Large B-Cell Lymphoma
  • Recurrent Follicular Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma
  • Refractory Follicular Lymphoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, rituximab)
RituximabABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83Treatment (pembrolizumab, rituximab)

Purpose

This phase II trial studies how well rituximab and pembrolizumab work in treating patients with follicular lymphoma or diffuse large B cell lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as pembrolizumab and rituximab, may interfere with the ability of cancer cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Overall response rate (ORR) of rituximab and pembrolizumab in relapsed/refractory
      follicular lymphoma (FL).

      II. Overall response rate (ORR) of rituximab and pembrolizumab in relapsed/refractory diffuse
      large B cell lymphoma (DLBCL).

      SECONDARY OBJECTIVES:

      I. To evaluate the safety and tolerability of the combination of rituximab and pembrolizumab,
      and of extended pembrolizumab administered for up to 1 year.

      II. To evaluate progression-free survival (PFS), and overall survival (OS) with this
      combination, in relapsed/refractory FL, and relapsed/refractory DLBCL.

      III. To explore treatment outcomes with this combination in patients with rituximab
      refractory FL.

      OUTLINE:

      INDUCTION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1.
      Patients also receive rituximab IV on days 1, 8, and 15 of course 1 and on day 1 of course 2.
      Courses repeat every 3 weeks for 4 courses in the absence of disease progression or
      unacceptable toxicity.

      EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30
      minutes on day 1. Courses repeat every 3 weeks for up to 2 years (35 doses) in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 90 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, rituximab)ExperimentalINDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive rituximab IV on days 1, 8, and 15 of course 1 and on day 1 of course 2. Courses repeat every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (35 doses) in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must have relapsed/refractory DLBCL or relapsed/refractory FL

               -  For DLBCL, patients must have relapsed after, declined, or considered ineligible
                  for high-dose chemotherapy and autologous stem cell transplantation

               -  For FL, in addition to relapsed/refractory disease status, patients must have
                  received therapy with CD20 antibody-directed therapy, and must have an indication
                  for treatment; FL eligibility also requires patients have no standard options
                  with curative potential, nor options with more favorable risk/benefit ratio in
                  the judgment of the investigator

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

          -  Have measurable disease (1.5 cm or greater in the longest diameter of nodal or
             extranodal disease)

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Within 28 days of cycle 1 day 1: Absolute neutrophil count (ANC) >= 1,000/mcL

          -  Within 28 days of cycle 1 day 1: Platelets >= 75,000/mcL

          -  Within 28 days of cycle 1 day 1: Hemoglobin >= 8 g/dL

          -  Within 28 days of cycle 1 day 1: 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

          -  Within 28 days of cycle 1 day 1: Serum total bilirubin =< 1.5 X ULN OR direct
             bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN

          -  Within 28 days of cycle 1 day 1: 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 involvement by lymphoma

          -  Within 28 days of cycle 1 day 1: Albumin >= 2.5 mg/dL

          -  Within 28 days of cycle 1 day 1: 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

          -  Within 28 days of cycle 1 day 1: Activated (a)PTT =< 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 must be willing to use an adequate method of
             contraception; contraception, for the course of the study through 120 days after the
             last dose of study medication

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject

          -  Male subjects of childbearing potential must 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

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject

        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, except for physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency which is permitted

          -  Has a known history of active TB (Bacillus tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier

          -  Prior allogeneic transplant, within the last 5 years

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
             baseline) from adverse events due to a previously administered agent

               -  Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study

               -  Note: If subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy

          -  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 lymphomatous
             meningitis; subjects with previously treated brain metastases or lymphomatous
             meningitis may participate provided they are stable (without evidence of progression
             by imaging for at least four weeks prior to the first dose of trial treatment and any
             neurologic symptoms have returned to baseline), have no evidence of new or enlarging
             brain metastases, and are not using steroids for at least 7 days prior to trial
             treatment

          -  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)

          -  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
Time Frame:Up to 90 days after the last dose of pembrolizumab
Safety Issue:
Description:Will be defined as the rate of complete + partial responses using computed tomography (CT) criteria (Lugano 2014).

Secondary Outcome Measures

Measure:Incidence of serious or drug-related adverse events
Time Frame:Up to 90 days after the last dose of pembrolizumab
Safety Issue:
Description:Evaluated by the NCI Common Terminology for Adverse Events (CTCAE), version 4.0.
Measure:Progression-free survival (PFS)
Time Frame:Up to 90 days after the last dose of pembrolizumab
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate median PFS.
Measure:Overall survival (OS)
Time Frame:Up to 90 days after the last dose of pembrolizumab
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate median OS.

Details

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

Last Updated

November 6, 2019