Clinical trial NCT05008224: Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11)
Official title: Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Classical Hodgkin Lymphoma
Keywords: Programmed Cell Death 1 (PD-1, PD1)
Programmed Cell Death-Ligand 1 (PD-L1, PDL1)
Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-08-17
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete Response (CR) Rate at the End of Study Intervention as Assessed by Blinded Independent Central Review (BICR) Per Lugano 2014 Response Criteria
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: CR Rate at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria
timeFrame: Up to approximately 31 months
measure: Duration of Complete Response (DurCR) as Assessed by BICR Per Lugano 2014 Response Criteria
timeFrame: Up to approximately 31 months
measure: Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy (PET Scan 2)
timeFrame: Up to approximately 10 weeks
measure: Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and AVD Chemotherapy (PET Scan 3)
timeFrame: Up to approximately 5 months
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 31 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 17 months
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: St Joseph Heritage Healthcare-Oncology ( Site 0004)
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center ( Site 0023)
state: California
city: Chicago
country: United States
facility: Northwestern Memorial Hospital ( Site 0002)
state: Illinois
city: Las Vegas
country: United States
facility: OptumCare Cancer Care-Research Department ( Site 0005)
state: Nevada
city: Knoxville
country: United States
facility: University of Tennessee Medical Center-Cancer Institute ( Site 0006)
state: Tennessee
city: Plano
country: United States
facility: Texas Oncology-Plano East ( Site 0020)
state: Texas
city: Liverpool
country: Australia
facility: Liverpool Hospital-Haematology ( Site 0906)
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Misericordiae Limited ( Site 0904)
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital-Division of Cancer Services Trials Unit ( Site 0907)
state: Queensland
city: Clayton
country: Australia
facility: Monash Health-Haematology Research ( Site 0908)
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre ( Site 0905)
state: Victoria
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0207)
state: Alberta
city: Greenfield Park
country: Canada
facility: Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 0205)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0200)
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal ( Site 0206)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre ( Site 0209)
state: Quebec
city: Temuco
country: Chile
facility: Centro Investigación del Cáncer James Lind ( Site 1200)
state: Araucania
city: Chile
country: Chile
facility: Instituto Nacional del Cancer ( Site 1205)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 1202)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Clínica Alemana de Santiago ( Site 1206)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1204)
state: Region M. De Santiago
city: Pessac
country: France
facility: CHU Bordeaux Haut-Leveque ( Site 1505)
state: Aquitaine
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou-haematology ( Site 1502)
state: Bretagne
city: Dijon
country: France
facility: Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 1504)
state: Cote-d Or
city: Pierre-Bénite
country: France
facility: centre hospitalier lyon sud-Service Hématologie ( Site 1501)
state: Rhone
city: Rouen
country: France
facility: Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen-Service d'Hématologie ( Si
state: Seine-Maritime
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 1907)
city: Haifa
country: Israel
facility: Bnai Zion Medical Center-Hematology ( Site 1909)
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 1901)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-Hemato Oncology ( Site 1904)
city: Safed
country: Israel
facility: ZIV Medical Center ( Site 1908)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1905)
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 1801)
state: Lombardia
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda ( Site 1803)
state: Milano
city: Bologna
country: Italy
facility: Policlinico S. Orsola- Malpighi-Istituto di Ematologia L. e A. Seragnoli ( Site 1800)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 1804)
city: Warsaw
country: Poland
facility: Klinika Hematologii - Instytut Hematologii i Transfuzjologii-Klinika Hematologii ( Site 0402)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
state: Mazowieckie
city: Opole
country: Poland
facility: Szpital Wojewódzki w Opolu-Hematology Department ( Site 0401)
state: Opolskie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0403)
state: Pomorskie
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital S.P. Botkin ( Site 0702)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: First Pavlov State Medical University of Saint Petersburg-Raisa Gorbacheva Memorial Institut for Pe
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Almazov National Medical Research Centre ( Site 0704)
state: Sankt-Peterburg
city: L'Hospitalet Del Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 1031)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 1032)
city: Balçova
country: Turkey
facility: Dokuz Eylül Üniversitesi ( Site 5002)
state: Izmir
city: Ankara
country: Turkey
facility: Ankara University Hospital Cebeci-hematology ( Site 5000)
city: Istanbul
country: Turkey
facility: Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 5001)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Allen PB, Lu X, Chen Q, O'Shea K, Chmiel JS, Slonim LB, Sukhanova M, Savas H, Evens AM, Advani R, Pro B, Karmali R, Palmer B, Bayer RA, Eisner RM, Mou E, Dillehay G, Gordon LI, Winter JN. Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. Blood Adv. 2023 Jun 27;7(12):2670-2676. doi: 10.1182/bloodadvances.2022008116.