NCT02576990 · CITED IN SOURCE DOCUMENTS

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)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2023-07-27

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

ORR Based on IWG Response Assessment Criteria by Investigator Assessment

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outcome · POSTED

Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Independent Central Review

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outcome · POSTED

Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Investigator Assessment

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outcome · POSTED

Duration of Response (DOR) Based on IWG Response Assessment Criteria by Independent Central Review in Participants With Responses

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outcome · POSTED

Duration of Response (DOR) Based on IWG Response Assessment Criteria by Investigator Assessment in Participants With Responses

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outcome · POSTED

Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Independent Central Review

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outcome · POSTED

Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Investigator Assessment

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Number of Participants Who Experienced an Adverse Event (AE)

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outcome · POSTED

Number of Participants Who Discontinued Study Drug Due to an AE

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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).
intervention Names
Biological: Pembrolizumab
label
Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)
type
EXPERIMENTAL
description
Participants with rrRS receive pembrolizumab 200 mg Q3W, IV for each 3-week cycle for up to a maximum of 35 administrations (approximately 2 years). Effective with Protocol Amendment 04, enrollment into this cohort was closed.
intervention Names
Biological: Pembrolizumab
label
Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS)
type
EXPERIMENTAL

interventions

arm Group Labels
Pembrolizumab: Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL)
Pembrolizumab: Relapsed or Refractory Richter Syndrome (rrRS)
description
IV infusion
name
Pembrolizumab
other Names
MK-3475
KEYTRUDA®
SCH 900475
type
BIOLOGICAL

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 80
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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 rrPMBCL. 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.
measure
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)

secondary Outcomes

description
The ORR was assessed by Investigator assessment utilizing the IWG response assessment criteria per Cheson 2007 of pembrolizumab in participants with rrPMBCL. 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 (CR or 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.
measure
ORR Based on IWG Response Assessment Criteria by Investigator Assessment
time Frame
Up to approximately 27 months (Database Cutoff Date: 28MAY2019)
description
PFS was defined as the time from first dose to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD 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.
measure
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)
description
PFS was defined as the time from the first dose to the first documented PD or death due to any cause, whichever occurs first. PD 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.
measure
Progression Free Survival (PFS) Based on IWG Response Assessment Criteria by Investigator Assessment
time Frame
Up to approximately 27 months (Database Cutoff Date: 28MAY2019)
description
The DOR was defined, only for the subgroup of participants who achieved a CR or PR by independent central review, as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of PD 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. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. The analysis consisted of Kaplan-Meier estimates. DOR 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.
measure
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)
description
The DOR was defined, only for the subgroup of participants who achieved a CR or PR by investigator assessment, as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of PD 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. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. The analysis consisted of Kaplan-Meier estimates. DOR 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.
measure
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)
description
The DCR was defined as the percentage of participants in the analysis population who have achieved a CR, PR or stable disease (SD) response prior to PD. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. SD is the failure to attain CR/PR or PD. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Participants with missing data were considered non-responders.
measure
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)
description
The DCR was defined as the percentage of participants in the analysis population who have achieved a CR, PR or SD response prior to PD. CR is the disappearance of all evidence of disease and PR is the regression of measurable disease and no new sites. SD is the failure to attain CR/PR or PD. PD is the appearance any new lesion or increase by ≥ 50% of previously involved site from nadir. Participants with missing data were considered non-responders.
measure
Disease Control Rate (DCR) Based on IWG Response Assessment Criteria by Investigator Assessment
time Frame
Up to approximately 27 months (Database Cutoff Date: 28MAY2019)
description
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).
measure
Overall Survival (OS)
time Frame
Up to approximately 27 months (Database Cutoff Date: 28MAY2019)
description
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. The number of participants who experienced an AE were reported.
measure
Number of Participants Who Experienced 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)
description
An 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. The number of participants who discontinued study drug due to an AE were reported.
measure
Number of Participants Who Discontinued Study Drug Due to an AE
time Frame
Up to approximately 27 months (Database Cutoff Date: 28MAY2019)

Full study description

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.

Source references

references

citation
Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Ozcan 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.
pmid
31609651
type
RESULT
citation
Armand P, Murawski N, Molin D, Zain J, Eichhorst B, Gulbas Z, Hawkes EA, Pagel JM, Phillips T, Ribrag V, Svoboda J, Stathis A, Chatterjee A, Orlowski R, Marinello P, Christian B. Pembrolizumab in relapsed or refractory Richter syndrome. Br J Haematol. 2020 Jul;190(2):e117-e120. doi: 10.1111/bjh.16762. Epub 2020 Jun 16. No abstract available.
pmid
32544980
type
RESULT
citation
Zinzani PL, Thieblemont C, Melnichenko V, Bouabdallah K, Walewski J, Majlis A, Fogliatto L, Garcia-Sancho AM, Christian B, Gulbas Z, Ozcan M, Perini GF, Ghesquieres H, Shipp MA, Thompson S, Chakraborty S, Marinello P, Armand P. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023 Jul 13;142(2):141-145. doi: 10.1182/blood.2022019340.
pmid
37130017
type
RESULT