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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02576990
Recruitment Status : Active, not recruiting
First Posted : October 15, 2015
Results First Posted : June 24, 2020
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE October 14, 2015
First Posted Date  ICMJE October 15, 2015
Results First Submitted Date  ICMJE May 26, 2020
Results First Posted Date  ICMJE June 24, 2020
Last Update Posted Date June 24, 2020
Actual Study Start Date  ICMJE December 2, 2015
Actual Primary Completion Date May 28, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2020)
Objective Response Rate (ORR) Based on International Working Group (IWG) Response Assessment Criteria Per Independent Central Review [ Time Frame: Up to approximately 27 months (Database Cutoff: 28MAY2019) ]
The ORR was assessed by independent central review utilizing the International Working Group [IWG] response assessment criteria per Cheson 2007 of pembrolizumab in participants with relapsed or refractory PMBCL. For participants with rrRS, IWG criteria with special considerations for RS was used for progression. The ORR was defined as the percentage of participants who had a response (complete response, CR or partial response, PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data were considered non-responders. In the rrPMBCL cohort, an exact binomial test was conducted versus a fixed historical control rate. For the rrPMBCL cohort, the ORR was estimated as well as a 95% 2-sided exact confidence interval (CI) using the Clopper-Pearson method whereas the rrRS cohort was estimated with a 90% 2-sided CI.
Original Primary Outcome Measures  ICMJE
 (submitted: October 14, 2015)
Overall Response Rate (ORR) by Independent Central Review [ Time Frame: Every 12 weeks for up to 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2020)
  • ORR Based on IWG Response Assessment Criteria by Investigator Assessment [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    The ORR was assessed by Investigator assessment utilizing the International Working Group [IWG] response assessment criteria per Cheson 2007 of pembrolizumab in participants with relapsed or refractory PMBCL. For participants with rrRS, IWG criteria with special considerations for RS was used for progression. The ORR was defined as the percentage of participants who had a response (complete response, CR or partial response, PR) prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Participants with missing data were considered non-responders. In the rrPMBCL cohort, an exact binomial test was conducted versus a fixed historical control rate.
  • Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Independent Central Review [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    PFS is defined as the time from first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Progressive disease is the appearance of any new lesion or increase by ≥ 50% of previously involved site from nadir. Calculated from the product-limit (Kaplan-Meier) method for censored data. Data was censored at the last assessment for sensitivity analyses based on alternative censoring.
  • Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Investigator Assessment [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    PFS is defined as the time from the first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Progressive disease is the appearance of any new lesion or increase by ≥ 50% of previously involved site from nadir. Calculated from the product-limit (Kaplan-Meier) method for censored data.
  • Duration of Response (DOR) Based on IWG Response Assessment Criteria by Independent Central Review in Participants With Responses [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    The DOR was defined, only for the subgroup of participants who achieved a complete response or partial response by independent central review, as the time from start of the first documentation of objective tumor response (complete response or partial response) to the first documentation of tumor progression or to death due to any cause, whichever comes first. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Progressive disease is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. The analysis consisted of Kaplan-Meier estimates. Duration of response data was censored on the date of the last disease assessment documenting absence of PD for participants who did not have tumor progression and were still on study at the time of an analysis, were given antitumor treatment other than the study treatment, or were removed from study prior to documentation of tumor progression.
  • Duration of Response (DOR) Based on IWG Response Assessment Criteria by Investigator Assessment in Participants With Responses [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    The DOR was defined, only for the subgroup of participants who achieved a complete response or partial response by investigator assessment, as the time from start of the first documentation of objective tumor response (complete response or partial response) to the first documentation of tumor progression or to death due to any cause, whichever comes first. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Progressive disease is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. The analysis consisted of Kaplan-Meier estimates. Duration of response data was censored on the date of the last disease assessment documenting absence of PD for participants who did not have tumor progression and were still on study at the time of an analysis, were given antitumor treatment other than the study treatment, or were removed from study prior to documentation of tumor progression.
  • Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Independent Central Review [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    The DCR, defined as the percentage of participants in the analysis population who have achieved a complete response, partial response or stable disease response prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Stable disease is the failure to attain CR/PR or PD. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Progressive disease is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Participants with missing data were considered non-responders.
  • Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Investigator Assessment [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    The DCR, defined as the percentage of participants in the analysis population who have achieved a complete response, partial response or stable disease response prior to disease progression. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. Stable disease is the failure to attain CR/PR or PD. Progressive disease is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Participants with missing data were considered non-responders.
  • Overall Survival (OS) [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    OS was defined as the time from the first dose to death due to any cause. OS is presented from product limit (Kaplan-Meier) method for censored data (censored at the last assessment).
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 30 months (Up to 90 days after last dose of study treatment) (Database Cutoff Date: 28MAY2019) ]
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
  • Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to approximately 27 months (Database Cutoff Date: 28MAY2019) ]
    An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Mediastinal Large B-cell Lymphoma
  • Richter Syndrome
Intervention  ICMJE Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Study Arms  ICMJE
  • 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).
    Intervention: Biological: Pembrolizumab
  • 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.
    Intervention: Biological: Pembrolizumab
Publications * Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. doi: 10.1200/JCO.19.01389. Epub 2019 Oct 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 15, 2017)
80
Original Estimated Enrollment  ICMJE
 (submitted: October 14, 2015)
53
Estimated Study Completion Date  ICMJE November 30, 2021
Actual Primary Completion Date May 28, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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-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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Australia,   Brazil,   Chile,   Colombia,   France,   Germany,   Italy,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   Turkey,   United States
 
Administrative Information
NCT Number  ICMJE NCT02576990
Other Study ID Numbers  ICMJE 3475-170
2015-002406-37 ( EudraCT Number )
MK-3475-170 ( Other Identifier: Merck Protocol Number )
KEYNOTE-170 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP