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

Classical Hodgkin Lymphoma Clinical Trial

— KEYNOTE-C11  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05008224
• Other study ID #: 3475-C11
• Secondary ID: MK-3475-C11KEYNO
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 7, 2021
• Est. completion date: May 22, 2024

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 146
• Est. completion date: May 22, 2024
• Est. primary completion date: October 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Classical Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma

Intervention

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.

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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  France,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response (CR) at the End of Study Intervention as Assessed by Independent Central Review (ICR) Per Lugano 2014 Response Criteria	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	CR at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria	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
Secondary	Duration of Complete Response (DurCR) as Assessed by Independent Central Review Per Lugano 2014 Response Criteria	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
Secondary	Positron Emission Tomography (PET) Negativity by Independent Central Review Per 3-Fluorodeoxyglucose (FDG)-PET 5-point Scale After Administration of Pembrolizumab Monotherapy	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
Secondary	PET Negativity by Independent Central Review Per FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy and Chemotherapy	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
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	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
Secondary	Number of Participants Who Discontinued Study Treatment Due to an AE	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

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary