Study of Safety and Efficacy of Pembrolizumab and Chemotherapy in Participants With Newly Diagnosed Classical Hodgkin Lymphoma (cHL) (MK-3475-C11/KEYNOTE-C11)
- Conditions
- Classical Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT05008224
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 146
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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Pembrolizumab After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Doxorubicin After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Vinblastine After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Dacarbazine After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Bleomycin After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Etoposide After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Cyclophosphamide After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Vincristine After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Procarbazine After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan. Pembrolizumab Monotherapy + AVD Chemotherapy/escBEACOPP Chemotherapy + Pembrolizumab Consolidation Prednisone After completing Positron Emission Tomography (PET) scan 1 during eligibility screening, participants received pembrolizumab monotherapy intravenous (IV) for three 3-week cycles followed by PET scan 2. Participants next received 2 phases of chemotherapy. In chemotherapy phase 1, all participants received doxorubicin in combination with vinblastine \& dacarbazine (AVD) IV for two 4-week cycles followed by PET scan 3. In chemotherapy phase 2, participants who were PET scan 3 negative, or positive and age ≥60 years, received up to 4 additional cycles of AVD IV, while participants who were PET scan 3 positive and age \<60 years received up to four 3-week cycles of escalated bleomycin in combination with etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, \& prednisone (escBEACOPP) IV. All participants then received pembrolizumab consolidation IV for four 6-week cycles followed by a final PET scan.
- Primary Outcome Measures
Name Time Method Complete Response (CR) Rate at the End of Study Intervention as Assessed by Blinded Independent Central Review (BICR) Per Lugano 2014 Response Criteria Up to approximately 24 months CR rate was assessed by BICR using Computed Tomography (CT) and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal 2-fluorodeoxyglucose \[FDG\] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Per protocol, participants who discontinued study intervention during pembrolizumab monotherapy, chemotherapy, or pembrolizumab consolidation, or are lost to follow-up, or receive any new non-study anticancer therapy prior to end of treatment were classified as non-responders. The percentage of participants who had CR after the completion of pembrolizumab consolidation is presented.
- Secondary Outcome Measures
Name Time Method CR Rate at the End of Study Intervention as Assessed by Investigator Per Lugano 2014 Response Criteria Up to approximately 31 months CR rate was assessed by the investigator using CT and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Per protocol, participants who discontinued study intervention during pembrolizumab monotherapy, chemotherapy, or pembrolizumab consolidation, or are lost to follow-up, or receive any new non-study anticancer therapy prior to end of treatment were classified as non-responders. The percentage of participants who had CR after the completion of pembrolizumab consolidation is presented.
Duration of Complete Response (DurCR) as Assessed by BICR Per Lugano 2014 Response Criteria Up to approximately 31 months DurCR was defined as the time from CR to progressive disease (PD) or death due to any cause, whichever came first. CR was assessed by BICR using CT and PET scan according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). At each timepoint, CR was determined by combining the anatomic response, metabolic response, and clinical data. The criteria for CR included complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. PD was defined as uptake moderately or markedly higher than the liver and/or new lesions. DurCR was analyzed by the Kaplan-Meier method for censored data and is presented for participants who demonstrated CR.
Rate of PET Negativity Assessed by BICR According to the FDG-PET 5-point Scale After Administration of Pembrolizumab Monotherapy (PET Scan 2) Up to approximately 10 weeks The rate of PET negativity was defined as the percentage of participants considered negative on the FDG-PET 5-point scale, as assessed by BICR according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). Participants were assigned a single score on the FDG-PET 5-point scale measuring FDG uptake (1 = no uptake above background, 2 = uptake above background but ≤ mediastinum, 3 = uptake \> mediastinum but ≤ liver, 4 = uptake moderately \> liver, 5 = uptake markedly \> liver or new FDG-positive lesions). Higher scores corresponded to greater uptake (greater disease). FDG-PET 5-point scale scores of 1, 2, and 3 were considered negative and scores of 4 and 5 were considered positive. The percentage of participants who were assessed as negative at PET scan 2, after completion of 3 cycles of pembrolizumab monotherapy, is presented.
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) Up to approximately 5 months The rate of PET negativity was defined as the percentage of participants considered negative on the FDG-PET 5-point scale, as assessed by BICR according to Lugano 2014 response criteria (Cheson, B.D. et al, Journal of Clinical Oncology, 2014). Participants were assigned a single score on the FDG-PET 5-point scale measuring FDG uptake (1 = no uptake above background, 2 = uptake above background but ≤ mediastinum, 3 = uptake \> mediastinum but ≤ liver, 4 = uptake moderately \> liver, 5 = uptake markedly \> liver or new FDG-positive lesions). Higher scores corresponded to greater uptake (greater disease). FDG-PET 5-point scale scores of 1, 2, and 3 were considered negative and scores of 4 and 5 were considered positive. The percentage of participants who were assessed as negative at PET scan 3, after completion of 3 cycles of pembrolizumab monotherapy and phase 1 AVD chemotherapy (2 AVD cycles), is presented.
Number of Participants Who Experienced an Adverse Event (AE) Up to approximately 31 months 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. Per protocol, collection and reporting of AEs was based on the study treatment received by the participant (pembrolizumab, AVD chemotherapy, or escBEACOPP chemotherapy) at the time of the event. The number of participants who experienced an AE is reported.
Number of Participants Who Discontinued Study Treatment Due to an AE Up to approximately 17 months 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. Per protocol, collection and reporting of AEs was based on the study treatment received by the participant (pembrolizumab, AVD chemotherapy, or escBEACOPP chemotherapy) at the time of the event. The number of participants who discontinued study intervention due to an AE is reported.
Trial Locations
- Locations (48)
Stanford Cancer Center ( Site 0023)
🇺🇸Palo Alto, California, United States
Northwestern Memorial Hospital ( Site 0002)
🇺🇸Chicago, Illinois, United States
Texas Oncology-Plano East ( Site 0020)
🇺🇸Plano, Texas, United States
Mater Misericordiae Limited ( Site 0904)
🇦🇺Brisbane, Queensland, Australia
Liverpool Hospital-Haematology ( Site 0906)
🇦🇺Liverpool, New South Wales, Australia
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
Instituto Nacional del Cancer ( Site 1205)
🇨🇱Chile, Region M. De Santiago, Chile
Centre Hospitalier Universitaire Dijon Bourgogne - Hôpital François Mitterrand ( Site 1504)
🇫🇷Dijon, Cote-d Or, France
Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 1204)
🇨🇱Santiago, Region M. De Santiago, Chile
CHU Bordeaux Haut-Leveque ( Site 1505)
🇫🇷Pessac, Aquitaine, France
centre hospitalier lyon sud-Service Hématologie ( Site 1501)
🇫🇷Pierre-Bénite, Rhone, France
Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen-Service d'Hématologie ( Si
🇫🇷Rouen, Seine-Maritime, France
Bnai Zion Medical Center-Hematology ( Site 1909)
🇮🇱Haifa, Israel
Sourasky Medical Center ( Site 1905)
🇮🇱Tel Aviv, Israel
Azienda Ospedaliera Spedali Civili di Brescia-Hemathology ( Site 1801)
🇮🇹Brescia, Lombardia, Italy
Policlinico S. Orsola- Malpighi-Istituto di Ematologia L. e A. Seragnoli ( Site 1800)
🇮🇹Bologna, Italy
Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 1804)
🇮🇹Roma, Italy
St Joseph Heritage Healthcare-Oncology ( Site 0004)
🇺🇸Fullerton, California, United States
Dokuz Eylül Üniversitesi ( Site 5002)
🇹🇷Balçova, Izmir, Turkey
Hospital Universitario 12 de Octubre ( Site 1032)
🇪🇸Madrid, Spain
Vehbi Koc Vakfi - Amerikan Hastanesi ( Site 5001)
🇹🇷Istanbul, Turkey
Jewish General Hospital ( Site 0200)
🇨🇦Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Rennes - Hôpital Pontchaillou-haematology ( Site 1502)
🇫🇷Rennes, Bretagne, France
Centro Investigación del Cáncer James Lind ( Site 1200)
🇨🇱Temuco, Araucania, Chile
FALP-UIDO ( Site 1202)
🇨🇱Santiago, Region M. De Santiago, Chile
Klinika Hematologii - Instytut Hematologii i Transfuzjologii-Klinika Hematologii ( Site 0402)
🇵🇱Warsaw, Mazowieckie, Poland
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 1031)
🇪🇸L'Hospitalet Del Llobregat, Barcelona, Spain
Peter MacCallum Cancer Centre ( Site 0905)
🇦🇺Melbourne, Victoria, Australia
Clínica Alemana de Santiago ( Site 1206)
🇨🇱Santiago, Region M. De Santiago, Chile
Hadassah Medical Center ( Site 1901)
🇮🇱Jerusalem, Israel
Sheba Medical Center-Hemato Oncology ( Site 1904)
🇮🇱Ramat Gan, Israel
Almazov National Medical Research Centre ( Site 0704)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Ankara University Hospital Cebeci-hematology ( Site 5000)
🇹🇷Ankara, Turkey
OptumCare Cancer Care-Research Department ( Site 0005)
🇺🇸Las Vegas, Nevada, United States
University of Tennessee Medical Center-Cancer Institute ( Site 0006)
🇺🇸Knoxville, Tennessee, United States
Princess Alexandra Hospital-Division of Cancer Services Trials Unit ( Site 0907)
🇦🇺Woolloongabba, Queensland, Australia
Monash Health-Haematology Research ( Site 0908)
🇦🇺Clayton, Victoria, Australia
McGill University Health Centre ( Site 0209)
🇨🇦Montréal, Quebec, Canada
Rambam Health Care Campus ( Site 1907)
🇮🇱Haifa, Israel
ASST Grande Ospedale Metropolitano Niguarda ( Site 1803)
🇮🇹Milan, Milano, Italy
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
🇵🇱Warszawa, Mazowieckie, Poland
Moscow City Clinical Hospital S.P. Botkin ( Site 0702)
🇷🇺Moscow, Moskva, Russian Federation
Szpital Wojewódzki w Opolu-Hematology Department ( Site 0401)
🇵🇱Opole, Opolskie, Poland
Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0403)
🇵🇱Gdańsk, Pomorskie, Poland
First Pavlov State Medical University of Saint Petersburg-Raisa Gorbacheva Memorial Institut for Pe
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
ZIV Medical Center ( Site 1908)
🇮🇱Safed, Israel