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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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ClinicalTrials.gov Identifier: NCT02576990
Recruitment Status : Active, not recruiting
First Posted : October 15, 2015
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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 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.


Condition or disease Intervention/treatment Phase
Mediastinal Large B-cell Lymphoma Richter Syndrome Biological: Pembrolizumab Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 2, 2015
Estimated Primary Completion Date : September 14, 2019
Estimated Study Completion Date : September 14, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Pembrolizumab: rrPMBCL
Participants with rrPMBCL receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to a maximum of 35 administrations (approximately 2 years).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Experimental: Pembrolizumab: rrRS
Participants with rrRS receive pembrolizumab 200 mg IV Q3W for up to a maximum of 35 administrations (approximately 2 years). Effective with Protocol Amendment 04, enrollment into this cohort was closed.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®




Primary Outcome Measures :
  1. Objective Response Rate (ORR) by Independent Central Review [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :
  1. ORR by Investigator Assessment [ Time Frame: Up to 2 years ]
  2. Progression Free Survival (PFS) by Independent Central Review and Investigator Assessment [ Time Frame: Up to 2 years ]
  3. Duration of Response (DOR) by Independent Central Review and Investigator Assessment [ Time Frame: Up to 2 years ]
  4. Disease Control Rate (DCR) by Independent Central Review and Investigator Assessment [ Time Frame: Up to 2 years ]
  5. Overall Survival (OS) [ Time Frame: Up to 2 years ]
  6. Number of Participants Who Experience an AE [ Time Frame: Up to 27 months ]
  7. Number of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • PMBCL:
  • Diagnosis of relapsed or refractory primary mediastinal large B-cell lymphoma 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.
  • RS:
  • Pathologic diagnosis per local institutional review of Richter syndrome that transformed from chronic lymphocytic leukemia (CLL).
  • Relapsed or refractory Richter syndrome and has received ≥1 previous treatment for RS.
  • All Participants:
  • Radiographically measureable 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-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.

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): NCT02576990


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02576990     History of Changes
Other Study ID Numbers: 3475-170
2015-002406-37 ( EudraCT Number )
MK-3475-170 ( Other Identifier: Merck Protocol Number )
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018

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

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Lymphoma
Syndrome
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Lymphoma, Non-Hodgkin
Pembrolizumab
Antineoplastic Agents