Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma or Relapsed or Refractory Richter Syndrome (MK-3475-170/KEYNOTE-170)

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Brief Title

Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma or Relapsed or Refractory Richter Syndrome (MK-3475-170/KEYNOTE-170)

Official Title

A Phase II Study of Pembrolizumab (MK-3475) in Subjects With Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL) or Relapsed or Refractory Richter Syndrome (rrRS)

Brief Summary

      In this study, participants with relapsed or refractory primary mediastinal large B-cell
      lymphoma (rrPMBCL) or relapsed or refractory Richter Syndrome (rrRS) will receive
      pembrolizumab (MK-3475). The efficacy of pembrolizumab in the treatment of rrPMBCL and rrRS
      will be evaluated. The primary study hypothesis is that intravenous (IV) administration of
      single agent pembrolizumab to the rrPMBCL cohort will result in an Objective Response Rate
      (ORR) of greater than 15% using the International Working Group (IWG) response criteria
      (Cheson, 2007) by independent central review.

      Effective with Protocol Amendment 04, enrollment into the rrRS cohort was closed.
    

Detailed Description

      Treatment with pembrolizumab will continue for a maximum of 35 administrations (approximately
      2 years) or until documented disease progression by investigator assessment, unacceptable
      adverse event(s) (AEs), intercurrent illness that prevents further administration of
      treatment, participant withdraws consent, pregnancy of the participant, noncompliance with
      study treatment or procedure requirements, or administrative reasons.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective Response Rate (ORR) Based on International Working Group (IWG) Response Assessment Criteria Per Independent Central Review

Secondary Outcome

 ORR Based on IWG Response Assessment Criteria by Investigator Assessment

Condition

Mediastinal Large B-cell Lymphoma

Intervention

Pembrolizumab

Study Arms / Comparison Groups

 Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)
Description:  Participants with rrPMBCL receive pembrolizumab 200 mg every 3 weeks (Q3W), intravenous infusion (IV) on Day 1 of each 3-week cycle for up to a maximum of 35 administrations (approximately 2 years).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

80

Start Date

December 2, 2015

Completion Date

October 23, 2020

Primary Completion Date

May 28, 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Primary mediastinal large B-cell lymphoma (PMBCL):

          -  Diagnosis of relapsed or refractory primary mediastinal large B-cell lymphoma
             (rrPMBCL) AND

          -  Has relapsed after autologous stem cell transplant (auto-SCT) or has failed to achieve
             a Complete Response or Partial Response within 60 days of auto-SCT. Participants may
             have received intervening therapy after auto-SCT for relapsed or refractory disease,
             in which case they must have relapsed after or be refractory to their last treatment
             OR

          -  For participants who are ineligible for auto-SCT, has received at least ≥2 lines of
             prior therapy and has failed to respond to or relapsed after their last line of
             treatment. For participants who received consolidative local radiotherapy after
             systemic therapy, local radiotherapy will not be considered as a separate line of
             treatment

          -  Previously exposed to rituximab as part of prior lines of treatment

          -  Richter syndrome (RS):

          -  Pathologic diagnosis per local institutional review of RS that transformed from
             chronic lymphocytic leukemia (CLL)

          -  Relapsed or refractory Richter syndrome and has received ≥1 previous treatment for RS

          -  All Participants:

          -  Radiographically measurable disease

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

          -  Life expectancy >3 months

          -  Adequate organ function

          -  Female participants of childbearing potential must be willing to use an adequate
             method of contraception for the course of the study through 120 days after the last
             dose of study drug

          -  Male participants of childbearing potential must agree to use an adequate method of
             contraception, starting with the first dose of study drug through 120 days after the
             last dose of study drug

        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 study drug

          -  Is receiving systemic steroid therapy <3 days before the first dose of study drug or
             receiving any other form of immunosuppressive medication

          -  Prior monoclonal antibody within 4 weeks prior to study Day 1 (2 weeks for RS
             participants) or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse
             events due to agents administered more than 4 weeks earlier (2 weeks for RS
             participants)

          -  Prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study
             Day 1 or prior radiation therapy within 4 weeks prior to study Day 1

          -  Allogeneic hematopoietic stem cell transplantation within the last 5 years.

          -  Has a known additional malignancy (except underlying CLL for RS) that is progressing
             or requires active treatment. Exceptions include basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone
             potentially curative therapy

          -  Known clinically active central nervous system involvement

          -  Active autoimmune disease requiring systemic treatment in past 2 years

          -  History of (non-infectious) pneumonitis that required steroids, or current pneumonitis

          -  Active infection requiring intravenous systemic therapy

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the pre-screening or screening visit
             through 120 days after the last dose of study drug

          -  Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),
             anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2
             (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
             antibody (including ipilimumab or any other antibody or drug specifically targeting
             T-cell co-stimulation or checkpoint pathways)

          -  Known human immunodeficiency virus (HIV), or Hepatitis B or C

          -  Has received a live vaccine within 30 days prior to first dose of study drug
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Medical Director, , 



Administrative Informations


NCT ID

NCT02576990

Organization ID

3475-170

Secondary IDs

2015-002406-37

Responsible Party

Sponsor

Study Sponsor

Merck Sharp & Dohme LLC


Study Sponsor

Medical Director, Study Director, Merck Sharp & Dohme LLC


Verification Date

October 2021