Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11) (KEYNOTE-C11)

January 29, 2024 updated by: Merck Sharp & Dohme LLC

Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11)

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab consolidation. The primary hypothesis of the study is that the complete response (CR) rate at the end of study intervention according to Lugano 2014 response criteria is higher than conventional chemotherapy.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

146

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital-Haematology ( Site 0906)
    • Queensland
      • Brisbane, Queensland, Australia, 4101
        • Mater Misericordiae Limited ( Site 0904)
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital-Division of Cancer Services Trials Unit ( Site 0907)
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health-Haematology Research ( Site 0908)
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre ( Site 0905)
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute ( Site 0207)
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 0205)
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital ( Site 0200)
      • Montreal, Quebec, Canada, H4J 1C5
        • Hopital du Sacre-Coeur de Montreal ( Site 0206)
      • Montréal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre ( Site 0209)
  • Chile
    • Araucania
      • Temuco, Araucania, Chile, 4780000
        • Centro Investigación del Cáncer James Lind ( Site 1200)
    • Region M. De Santiago
      • Chile, Region M. De Santiago, Chile, 8380455
        • Instituto Nacional del Cancer ( Site 1205)
      • Santiago, Region M. De Santiago, Chile, 6900941
        • FALP-UIDO ( Site 1202)
      • Santiago, Region M. De Santiago, Chile, 8320325
        • Clínica Alemana de Santiago ( Site 1206)
      • Santiago, Region M. De Santiago, Chile, 8330032
        • Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1204)
  • France
    • Aquitaine
      • Pessac, Aquitaine, France, 33600
        • CHU Bordeaux Haut-Leveque ( Site 1505)
    • Bretagne
      • Rennes, Bretagne, France, 35033
        • Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou-haematology ( Site 1502)
    • Cote-d Or
      • Dijon, Cote-d Or, France, 21000
        • Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 1504)
    • Rhone
      • Pierre-Bénite, Rhone, France, 69310
        • centre hospitalier lyon sud-Service Hématologie ( Site 1501)
    • Seine-Maritime
      • Rouen, Seine-Maritime, France, 76000
        • Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen-Service d'Hématologie ( Si
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus ( Site 1907)
      • Haifa, Israel, 3339419
        • Bnai Zion Medical Center-Hematology ( Site 1909)
      • Jerusalem, Israel, 9112001
        • Hadassah Medical Center ( Site 1901)
      • Ramat Gan, Israel, 5265601
        • Sheba Medical Center-Hemato Oncology ( Site 1904)
      • Safed, Israel, 1311001
        • ZIV Medical Center ( Site 1908)
      • Tel Aviv, Israel, 6423906
        • Sourasky Medical Center ( Site 1905)
  • Italy
      • Bologna, Italy, 40138
        • Policlinico S. Orsola- Malpighi-Istituto di Ematologia L. e A. Seragnoli ( Site 1800)
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 1804)
    • Lombardia
      • Brescia, Lombardia, Italy, 25123
        • Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 1801)
    • Milano
      • Milan, Milano, Italy
        • ASST Grande Ospedale Metropolitano Niguarda ( Site 1803)
  • Poland
    • Mazowieckie
      • Warsaw, Mazowieckie, Poland, 02-776
        • Klinika Hematologii - Instytut Hematologii i Transfuzjologii-Klinika Hematologii ( Site 0402)
      • Warszawa, Mazowieckie, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
    • Opolskie
      • Opole, Opolskie, Poland, 46-020
        • Szpital Wojewódzki w Opolu-Hematology Department ( Site 0401)
    • Pomorskie
      • Gdańsk, Pomorskie, Poland, 80-952
        • Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0403)
  • Russian Federation
    • Moskva
      • Moscow, Moskva, Russian Federation, 125284
        • Moscow City Clinical Hospital S.P. Botkin ( Site 0702)
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197022
        • First Pavlov State Medical University of Saint Petersburg-Raisa Gorbacheva Memorial Institut for Pe
      • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197341
        • Almazov National Medical Research Centre ( Site 0704)
  • Spain
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre ( Site 1032)
    • Barcelona
      • L'Hospitalet Del Llobregat, Barcelona, Spain, 08908
        • Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 1031)
  • Turkey
      • Ankara, Turkey, 06100
        • Ankara University Hospital Cebeci-hematology ( Site 5000)
      • Istanbul, Turkey, 34365
        • Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 5001)
    • Izmir
      • Balçova, Izmir, Turkey
        • Dokuz Eylül Üniversitesi ( Site 5002)
  • United States
    • California
      • Fullerton, California, United States, 92835
        • St Joseph Heritage Healthcare-Oncology ( Site 0004)
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Center ( Site 0023)
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital ( Site 0002)
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • OptumCare Cancer Care-Research Department ( Site 0005)
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center-Cancer Institute ( Site 0006)
    • Texas
      • Plano, Texas, United States, 75075
        • Texas Oncology-Plano East ( Site 0020)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

The main inclusion criteria include, but are not limited to the following:

  • Has a histologically confirmed diagnosis of Ann Arbor Stage III or IV classical Hodgkin Lymphoma (cHL). Stage I and II participants may be enrolled, but must have at least one National Comprehensive Cancer Network (NCCN) unfavorable risk factor per protocol
  • Has measurable 2-fluorodeoxyglucose (FDG)-avid disease based on investigator assessment according to Lugano 2014 response criteria
  • Has not received prior radiation therapy, chemotherapy, immunotherapy, or other systemic therapy for the treatment of cHL before the first dose of study intervention
  • Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 assessed within 7 days before the start of study intervention

Exclusion Criteria:

The main exclusion criteria include, but are not limited to the following:

  • Has confirmed nodular lymphocyte-predominant Hodgkin Lymphoma (HL)
  • Has an uncontrolled intercurrent cardiovascular illness
  • Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death ligand 1 protein (PD-L1), or anti- programmed cell death ligand 2 protein (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  • Has received or is expected to receive a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
  • Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has a history or current evidence of pulmonary fibrosis
  • Has had an allogenic tissue/solid organ transplant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab Monotherapy + Chemotherapy + Pembrolizumab Consolidation

Participants receive pembrolizumab monotherapy followed by chemotherapy with doxorubicin in combination with vinblastine & dacarbazine (AVD) or chemotherapy with escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, & prednisone (escBEACOPP) followed by pembrolizumab consolidation.

All participants receive pembrolizumab monotherapy intravenous (IV) for 3 cycles (cycle length = 3 weeks (wks); up to 9 wks). All participants receive AVD IV for 2 cycles (cycle length = 4 wks; up to 8 wks) after Positron Emission Tomography (PET) 2. Participants who are PET 3 -ve, or +ve & age ≥ 60 years, receive up to 4 additional cycles of AVD IV (cycle length = 4 wks, up to 16 wks), or up to 4 cycles of escBEACOPP IV if PET 3 +ve, age <60 years; cycle length = 3 wks; up to 12 wks. All participants receive pembrolizumab consolidation IV for 4 cycles (cycle length = 6 wks; up to 24 wks). Total treatment duration is up to 57 wks.
Biological: Pembrolizumab

200 mg IV administered on Day 1 of each 3-week cycle for 3 cycles during pembrolizumab monotherapy.

400 mg IV administered on Day 1 of each 6-week cycle for 4 cycles as pembrolizumab consolidation.

Other Names:
  • MK-3475
  • SCH 900475
  • KEYTRUDA®
Drug: Doxorubicin

25 mg/m^2 IV administered on Days 1 and 15 of each 4-week cycle for 2 cycles in all participants after PET2 and up to 4 additional cycles after PET3 (participants who are PET3 -ve, or +ve & ≥60 years of age).

35 mg/m^2 IV administered on Day 1 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve, <60 years of age).

Other Names:
  • Adriamycin
  • DOXIL®
  • Rubex®
Drug: Vinblastine
6 mg/m^2 IV administered on Days 1 and 15 of each 4-week cycle for 2 cycles after PET2 (all participants) and up to 4 additional cycles after PET3 (participants who are PET3 -ve, or +ve & ≥60 years of age).
Other Names:
  • Velban®
  • Alkaban-AQ®
Drug: Dacarbazine
375 mg/m^2 IV on Days 1 and 15 of each 4-week cycle for 2 cycles after PET2 (all participants) and up to 4 additional cycles after PET3 (participants who are PET3 -ve, or +ve & ≥60 years of age).
Other Names:
  • Dtic-Dome®
Drug: Bleomycin
10 units/m^2 IV administered on Day 8 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
  • Blenoxane®
Drug: Etoposide
200 mg/m^2 IV administered on Days 1-3 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
  • VP-16
  • VePesid®
  • Etopophos®
  • Toposar®
  • Etoposide phosphate
Drug: Cyclophosphamide
1250 mg/m^2 IV administered on Day 1 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
  • Cytoxan®
  • Neosar®
Drug: Vincristine
1.4 mg/m^2 IV on Day 8 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve &<60 years of age).
Other Names:
  • Oncovin®
  • Vincasar PFS®
Drug: Procarbazine
100 mg/m^2 orally (PO) administered on Days 1-7 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
  • Matulane®
Drug: Prednisone
40 mg/m^2 PO administered on Days 1-14 of each 3-week cycle for up to 4 cycles after PET3 (participants who are PET3 +ve & <60 years of age).
Other Names:
  • Deltasone®
  • Orasone®
  • Liquid Pred®
  • Meticorten®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response (CR) at the End of Study Intervention as Assessed by Independent Central Review (ICR) Per Lugano 2014 Response Criteria
Time Frame: Up to approximately 57 weeks
The percentage of participants who have CR at the end of study intervention, after the completion of pembrolizumab consolidation, as assessed by ICR per Lugano 2014 response criteria will be presented.
Up to approximately 57 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CR at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria
Time Frame: Up to approximately 57 weeks
The percentage of participants who have CR at the end of study intervention, after the completion of pembrolizumab consolidation, as assessed by the investigator per Lugano 2014 response criteria will be presented.
Up to approximately 57 weeks
Duration of Complete Response (DurCR) as Assessed by Independent Central Review Per Lugano 2014 Response Criteria
Time Frame: Up to approximately 72 months
DurCR is defined, only for the subgroup of participants who achieve CR, as the time from the first documentation of CR to disease progression or to death due to any cause, whichever comes first as assessed by the independent central review per Lugano 2014 response criteria.
Up to approximately 72 months
Positron Emission Tomography (PET) Negativity by Independent Central Review Per 3-Fluorodeoxyglucose (FDG)-PET 5-point Scale After Administration of Pembrolizumab Monotherapy
Time Frame: Up to approximately 9 weeks
The rate of PET negativity is defined as the percentage of participants with a score of 1, 2, or 3, assessed by independent central review according to the FDG-PET 5-point scale, after administration of pembrolizumab monotherapy. Per FDG-PET 5-point scale: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately higher than liver, Score 5= Uptake markedly higher than liver or new lesions. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.
Up to approximately 9 weeks
PET Negativity by Independent Central Review Per FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and Chemotherapy
Time Frame: Up to approximately 17 weeks
The rate of PET negativity is defined as the percentage of participants with a score of 1, 2, or 3, assessed by independent central review according to the FDG-PET 5-point scale, after administration of pembrolizumab monotherapy and chemotherapy. Per FDG-PET 5-point scale: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately higher than liver, Score 5= Uptake markedly higher than liver or new lesions. In the present study, scores of 1, 2 and 3 are considered to be negative and scores of 4 and 5 are considered to be positive.
Up to approximately 17 weeks
Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to approximately 64 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.
Up to approximately 64 weeks
Number of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: Up to approximately 57 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
Up to approximately 57 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2021

Primary Completion (Actual)

October 11, 2023

Study Completion (Estimated)

May 22, 2024

Study Registration Dates

First Submitted

August 13, 2021

First Submitted That Met QC Criteria

August 13, 2021

First Posted (Actual)

August 17, 2021

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-C11
  • MK-3475-C11 (Other Identifier: Merck)
  • KEYNOTE-C11 (Other Identifier: Merck)
  • 2021-001244-95 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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