Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)
Hodgkin Lymphoma
About this trial
This is an interventional treatment trial for Hodgkin Lymphoma focused on measuring Programmed Death-1 (PD-1), PD1, Programmed Death-Ligand 1 (PD-L1), PDL1
Eligibility Criteria
Inclusion Criteria:
- Group 1: Must have newly diagnosed, pathologically confirmed classical Hodgkin Lymphoma (cHL) at Stages IA, IB and IIA without bulky disease. Group 2: Must have newly diagnosed, pathologically confirmed cHL at Stages IIEB, IIIEA,IIIEB, IIIB, IVA and IVB
- Has measurable disease per investigator assessment
- Male participants are eligible to participate if they agree to the following during the intervention period: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per protocol unless confirmed to be azoospermic
- Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception during the intervention period and for at least 120 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period
- Performance status: Lansky Play-Performance Scale ≥50 for children up to 16 years of age OR Karnofsky score ≥50 for participants ≥ 16 years of age
- Has adequate organ function
Exclusion Criteria:
- Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years
- WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment
- Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%
- Has received prior therapy with an anti-Programmed Death (PD)-1, anti-Programmed Death-Ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a MSD pembrolizumab (MK-3475) clinical study
- Has received any prior systemic anti-cancer therapy,including investigational agents for current diagnosis before randomization
- Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
- Has a diagnosis of lymphocyte-predominant Hodgkin Lymphoma (HL)
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
- Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
- Has radiographically detectable central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
- Has severe hypersensitivity (≥Grade 3) to any study therapies including any excipients
- An active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
- Participants who have not adequately recovered from major surgery or have ongoing surgical complications
Sites / Locations
- Children's Hospital of Alabama ( Site 0023)
- Phoenix Childrens Hospital ( Site 0034)
- Arkansas Children's Hospital ( Site 0046)
- Kaiser - Orange County ( Site 0084)
- Kaiser Permanente ( Site 0082)
- Kaiser - Fontana ( Site 0083)
- MemorialCare Health System - Long Beach Medical Center-Cherese Mari Laulhere Children's Village ( Si
- Kaiser Permanente Downey Medical Center ( Site 0024)
- Kaiser Permanente - Oakland ( Site 0047)
- Kaiser Permanente - Roseville ( Site 0080)
- Kaiser Permanente - Santa Clara ( Site 0079)
- Children's Hospital - Colorado ( Site 0028)
- Connecticut Children's Medical Center ( Site 0045)
- Yale Cancer Center ( Site 0061)
- Children's National Medical Center ( Site 0090)
- University of Florida ( Site 0051)
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital ( Site 0048)
- Arnold Palmer Hospital ( Site 0065)
- Children's Healthcare of Atlanta at Egleston ( Site 0033)
- University of Chicago ( Site 0066)
- Riley Hospital for Children ( Site 0091)
- University of Kentucky Markey Cancer Center ( Site 0057)
- University of Louisville-Norton Children's Hospital ( Site 0059)
- Johns Hopkins University ( Site 0025)
- Children's Hospital of Michigan ( Site 0056)
- Karmanos Cancer Institute ( Site 0002)
- Children's Hospitals and Clinics of Minnesota ( Site 0036)
- St. Louis Children's Hospital ( Site 0038)
- Alliance for Childhood Diseases ( Site 0064)
- Hackensack University Medical Center ( Site 0026)
- Rutgers Cancer Institute of New Jersey ( Site 0027)
- Roswell Park Cancer Institute ( Site 0040)
- Cohen Children's Medical Center of New York ( Site 0052)
- Columbia University/Herbert Irving Cancer Center ( Site 0063)
- Memorial Sloan Kettering Cancer Center ( Site 0060)
- Weill Cornell Medicine ( Site 0032)
- UNC Lineberger Comprehensive Cancer ( Site 0044)
- Cincinnati Children's Hospital Medical Center ( Site 0035)
- Nationwide Children's Hospital ( Site 0037)
- St. Francis Hospital Cancer Center ( Site 0001)
- Vanderbilt University Medical Center-Ingram Cancer Center ( Site 0054)
- Dell Children's Medical Center Of Central Texas ( Site 0058)
- Children's Medical Center ( Site 0030)
- Texas Children's Hospital ( Site 0042)
- Methodist HealthCare System of San Antonio Clinical Trials Office, Texas Transplant Institute ( Site
- Inova Fairfax Hospital ( Site 0031)
- Seattle Childrens Hospital ( Site 0022)
- Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 0507)
- Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0510)
- Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0500)
- Hospital Pablo Tobon Uribe-Hematology ( Site 0565)
- Organizacion Clinica Bonnadona-Prevenir S.A.S. ( Site 0529)
- Oncomédica S.A.S ( Site 0527)
- Instituto Nacional De Cancerologia ( Site 0566)
- Fakultni nemocnice v Motole ( Site 0356)
- CHU de Marseille Hopital de la Timone Enfants ( Site 0449)
- CHU de Bordeaux. Hopital Pellegrin ( Site 0447)
- Hôpital Jeanne de Flandre ( Site 0450)
- Institut d'Hematologie-Oncologie Pediatrique (IHOP) ( Site 0448)
- Institut Gustave Roussy ( Site 0445)
- Hopital d'Enfants Armand Trousseau ( Site 0443)
- Hopital Universitaire Robert Debre ( Site 0446)
- Klinikum der Universitaet Muenchen-Campus Innenstadt ( Site 0414)
- Universitaetsklinikum Giessen und Marburg GmbH ( Site 0411)
- Universitaetsklinikum Essen ( Site 0415)
- Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Sit
- Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 0413)
- Athens Childrens Hospital Aglaia Kyriakou ( Site 0361)
- University of Athens - Aghia Sophia Childrens Hospital ( Site 0362)
- University General Hospital of Thessaloniki "AHEPA" ( Site 0363)
- Oncomedica ( Site 0545)
- Unidad Nacional de Oncologia Pediatrica ( Site 0542)
- Medi-K Cayala ( Site 0544)
- Universita degli Studi di Roma La Sapienza ( Site 0403)
- Centro di Riferimento Oncologico CRO ( Site 0404)
- Azienda Ospedaliera Santobono - Pausilipon ( Site 0402)
- IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0400)
- Ospedale Infantile Regina Margherita ( Site 0401)
- Severance Hospital Yonsei University Health System ( Site 0221)
- Samsung Medical Center ( Site 0222)
- Hospital Infantil de Mexico Federico Gomez ( Site 0535)
- Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0531)
- UMAE Hospital de Especialidades - CMN La Raza ( Site 0536)
- Hematologica Alta Especialidad ( Site 0532)
- Prinses Maxima Centrum ( Site 0461)
- Narodny ustav detskych chorob ( Site 0372)
- Wits Clinical Research ( Site 0323)
- Albert Alberts Stem Cell Transplant Centre ( Site 0324)
- Wits Clinical Research ( Site 0321)
- Hospital Universitari Vall d Hebron ( Site 0432)
- Hospital Infantil Universitario Nino Jesus ( Site 0433)
- Hospital Universitario La Paz ( Site 0434)
- University College London Hospitals NHS Foundation Trust ( Site 0454)
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Pembrolizumab + AVD (Group 1)
Pembrolizumab + COPDAC-28 (Group 2)
After receiving two 4-week cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) induction therapy, SER participants in Group 1 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) on Day 1 of each 3-week cycle (Q3W) in combination with two cycles of AVD chemotherapy (doxorubicin 25 mg/m^2, vinblastine 6 mg/m^2 and dacarbazine 375 mg/m^2 on Days 1 and 15; cycle frequency every 4 weeks [Q4W]). All SERs in Group 1 will receive radiotherapy (RT) after completing AVD chemotherapy.
After receiving two 4-week cycles of OEPA (vincristine, etoposide/etopophos, prednisone/prednisolone and doxorubicin) induction therapy, SER participants in Group 2 will receive pembrolizumab 2 mg/kg up to a maximum of 200 mg (3 to 17 years of age) or 200 mg (18 to 25 years of age) Q3W, in combination with 4 cycles of COPDAC-28 chemotherapy (cyclophosphamide 500 mg/m^2 on Days 1 and 8, vincristine 1.5 mg/m^2 with maximum single dose 2 mg on Days 1 and 8, prednisone/prednisolone 40 mg/m^2/day divided in 3 doses on Days 1 to 15, dacarbazine 250 mg/m^2 on Days 1 to 3; cycle frequency Q4W). SERs in Group 2 will receive RT if they have a positive Positron Emission Tomography (PET) response after completing COPDAC-28 chemotherapy.