Clinical trial NCT03407144: Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)
Official title: An Open-label, Uncontrolled, Multicenter Phase II Trial of MK-3475 (Pembrolizumab) in Children and Young Adults With Newly Diagnosed Classical Hodgkin Lymphoma With Inadequate (Slow Early) Response to Frontline Chemotherapy (KEYNOTE 667)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: Programmed Death-1 (PD-1)
PD1
Programmed Death-Ligand 1 (PD-L1)
PDL1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 340
Sex: ALL
Minimum age (years): 3
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine the safety and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy in children and young adults with newly diagnosed classical Hodgkin Lymphoma (cHL) who are slow early responders (SERs) to frontline chemotherapy.

Detailed description: Group 1 will consist of low-risk participants with cHL Stages IA, IB and IIA without bulky disease. Group 2 will consist of high-risk participants with cHL Stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB.

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

Primary outcomes:
measure: Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 8 years
Secondary outcomes:
measure: Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy
timeFrame: Up to approximately 8 years
measure: Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR
timeFrame: Up to approximately 8 years
measure: Overall Survival (OS) in SER Participants By Risk Group (Low, High)
timeFrame: Up to approximately 8 years
measure: Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)
timeFrame: Up to approximately 8 years
measure: Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy
timeFrame: Up to approximately 8 years
measure: EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator
timeFrame: Up to approximately 8 years
measure: OS in RER Participants By Risk Group (Low, High)
timeFrame: Up to approximately 8 years
measure: Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High)
timeFrame: Up to approximately 8 years
measure: Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High)
timeFrame: Up to approximately 8 years
measure: Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High)
timeFrame: Up to approximately 8 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama ( Site 0023)
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital ( Site 0034)
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital ( Site 0046)
state: Arkansas
city: Anaheim
country: United States
facility: Kaiser - Orange County ( Site 0084)
state: California
city: Downey
country: United States
facility: Kaiser Permanente ( Site 0082)
state: California
city: Fontana
country: United States
facility: Kaiser - Fontana ( Site 0083)
state: California
city: Long Beach
country: United States
facility: MemorialCare Health System - Long Beach Medical Center-Cherese Mari Laulhere Children's Village ( Si
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Downey Medical Center ( Site 0024)
state: California
city: Oakland
country: United States
facility: Kaiser Permanente - Oakland ( Site 0047)
state: California
city: Roseville
country: United States
facility: Kaiser Permanente - Roseville ( Site 0080)
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente - Santa Clara ( Site 0079)
state: California
city: Aurora
country: United States
facility: Children's Hospital - Colorado ( Site 0028)
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center ( Site 0045)
state: Connecticut
city: New Haven
country: United States
facility: Yale Cancer Center ( Site 0061)
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center ( Site 0090)
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida ( Site 0051)
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital/Joe DiMaggio Children's Hospital ( Site 0048)
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital ( Site 0065)
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston ( Site 0033)
state: Georgia
city: Chicago
country: United States
facility: University of Chicago ( Site 0066)
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children ( Site 0091)
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center ( Site 0057)
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville-Norton Children's Hospital ( Site 0059)
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University ( Site 0025)
state: Maryland
city: Detroit
country: United States
facility: Children's Hospital of Michigan ( Site 0056)
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute ( Site 0002)
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota ( Site 0036)
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital ( Site 0038)
state: Missouri
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases ( Site 0064)
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center ( Site 0026)
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey ( Site 0027)
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute ( Site 0040)
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center of New York ( Site 0052)
state: New York
city: New York
country: United States
facility: Columbia University/Herbert Irving Cancer Center ( Site 0063)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center ( Site 0060)
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine ( Site 0032)
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer ( Site 0044)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0035)
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital ( Site 0037)
state: Ohio
city: Greenville
country: United States
facility: St. Francis Hospital Cancer Center ( Site 0001)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center-Ingram Cancer Center ( Site 0054)
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center Of Central Texas ( Site 0058)
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center ( Site 0030)
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital ( Site 0042)
state: Texas
city: San Antonio
country: United States
facility: Methodist HealthCare System of San Antonio Clinical Trials Office, Texas Transplant Institute ( Site
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Hospital ( Site 0031)
state: Virginia
city: Seattle
country: United States
facility: Seattle Childrens Hospital ( Site 0022)
state: Washington
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 0507)
state: Parana
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0510)
state: Rio Grande Do Norte
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0500)
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe-Hematology ( Site 0565)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Organizacion Clinica Bonnadona-Prevenir S.A.S. ( Site 0529)
state: Atlantico
city: Monteria
country: Colombia
facility: Oncomédica S.A.S ( Site 0527)
state: Cordoba
city: Bogotá
country: Colombia
facility: Instituto Nacional De Cancerologia ( Site 0566)
state: Distrito Capital De Bogota
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole ( Site 0356)
city: Marseille
country: France
facility: CHU de Marseille Hopital de la Timone Enfants ( Site 0449)
state: Bouches-du-Rhone
city: Bordeaux
country: France
facility: CHU de Bordeaux. Hopital Pellegrin ( Site 0447)
state: Gironde
city: Lille
country: France
facility: Hôpital Jeanne de Flandre ( Site 0450)
state: Nord
city: Lyon
country: France
facility: Institut d'Hematologie-Oncologie Pediatrique (IHOP) ( Site 0448)
state: Rhone-Alpes
city: Villejuif
country: France
facility: Institut Gustave Roussy ( Site 0445)
state: Val-de-Marne
city: Paris
country: France
facility: Hopital d'Enfants Armand Trousseau ( Site 0443)
city: Paris
country: France
facility: Hopital Universitaire Robert Debre ( Site 0446)
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen-Campus Innenstadt ( Site 0414)
state: Bayern
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH ( Site 0411)
state: Hessen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 0415)
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Sit
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 0413)
city: Athens
country: Greece
facility: Athens Childrens Hospital Aglaia Kyriakou ( Site 0361)
state: Attiki
city: Athens
country: Greece
facility: University of Athens - Aghia Sophia Childrens Hospital ( Site 0362)
state: Attiki
city: Thessaloniki
country: Greece
facility: University General Hospital of Thessaloniki "AHEPA" ( Site 0363)
state: Kentriki Makedonia
city: Guatemala
country: Guatemala
facility: Oncomedica ( Site 0545)
city: Guatemala
country: Guatemala
facility: Unidad Nacional de Oncologia Pediatrica ( Site 0542)
city: Guatemala
country: Guatemala
facility: Medi-K Cayala ( Site 0544)
city: Roma
country: Italy
facility: Universita degli Studi di Roma La Sapienza ( Site 0403)
state: Abruzzo
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico CRO ( Site 0404)
state: Pordenone
city: Napoli
country: Italy
facility: Azienda Ospedaliera Santobono - Pausilipon ( Site 0402)
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0400)
city: Torino
country: Italy
facility: Ospedale Infantile Regina Margherita ( Site 0401)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0221)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0222)
city: Mexico D.F.
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez ( Site 0535)
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0531)
state: Nuevo Leon
city: Azcapotzalco
country: Mexico
facility: UMAE Hospital de Especialidades - CMN La Raza ( Site 0536)
city: Huixquilucan
country: Mexico
facility: Hematologica Alta Especialidad ( Site 0532)
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum ( Site 0461)
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob ( Site 0372)
state: Bratislavsky Kraj
city: Johannesburg
country: South Africa
facility: Wits Clinical Research ( Site 0323)
state: Gauteng
city: Pretoria
country: South Africa
facility: Albert Alberts Stem Cell Transplant Centre ( Site 0324)
state: Gauteng
city: Soweto
country: South Africa
facility: Wits Clinical Research ( Site 0321)
state: Gauteng
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron ( Site 0432)
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus ( Site 0433)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0434)
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust ( Site 0454)
state: London, City Of
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: