Safety and Efficacy of Pembrolizumab (MK-3475) in Children and Young Adults With Classical Hodgkin Lymphoma (MK-3475-667/KEYNOTE-667)

NCT03407144 | Active Not Recruiting Phase 2 FDA Drug

• 5 other identifiers: 3475-667MK-3475-6672023-504821-38-00U1111-1289-83732017-001123-53
• Study Type: interventional
• Target: 340
• Locations: 16 countries
• Sites: 93

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.

Conditions

Hodgkin Lymphoma

Keywords

Programmed Death-1 (PD-1); PD1; Programmed Death-Ligand 1 (PD-L1); PDL1

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as Assessed by Blinded Independent Central Review (BICR)

  ORR is defined as the percentage of SER participants who have a Complete Response (\[CR\], disappearance of all evidence of disease) or Partial Response (\[PR\], regression of measurable disease and no new sites) using IWG revised response criteria and determined by BICR. The ORR will be estimated by risk group in SER participants.

  Up to approximately 8 years

Secondary Outcomes (10)

• Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy

  Up to approximately 8 years

• Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR

  Up to approximately 8 years

• Overall Survival (OS) in SER Participants By Risk Group (Low, High)

  Up to approximately 8 years

• Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)

  Up to approximately 8 years

• Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy

  Up to approximately 8 years

Study Arms (2)

Pembrolizumab + AVD (Group 1)

EXPERIMENTAL

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.

Biological: pembrolizumab; Drug: doxorubicin; Drug: vinblastine; Drug: dacarbazine; Drug: bleomycin; Radiation: Radiotherapy (RT)

Pembrolizumab + COPDAC-28 (Group 2)

EXPERIMENTAL

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.

Biological: pembrolizumab; Drug: doxorubicin; Drug: dacarbazine; Drug: cyclophosphamide; Drug: vincristine; Drug: prednisone/prednisolone; Drug: etoposide; Radiation: Radiotherapy (RT)

Interventions

doxorubicin DRUG

25 mg/m\^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 40 mg/m\^2 IV on Days 1 and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 25 mg/m\^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1)

Pembrolizumab + AVD (Group 1); Pembrolizumab + COPDAC-28 (Group 2)

vinblastine DRUG

6 mg/m\^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 6 mg/m\^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1)

Pembrolizumab + AVD (Group 1)

dacarbazine DRUG

375 mg/m\^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1) 375 mg/m\^2 IV on Days 1 and 15 as part of AVD chemotherapy (cycle frequency: Q4W, Group 1) 250 mg/m\^2 IV on Days 1 to 3 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)

Pembrolizumab + AVD (Group 1); Pembrolizumab + COPDAC-28 (Group 2)

vincristine DRUG

1.5 mg/m\^2 IV with maximum single dose 2 mg on Days 1, 8, and 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 1.5 mg/m\^2 IV with maximum single dose 2 mg on Days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)

Pembrolizumab + COPDAC-28 (Group 2)

prednisone/prednisolone DRUG

60 mg/m\^2/day orally divided in 3 doses on Days 1 to 15 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2) 40 mg/m\^2/day orally divided in 3 doses on Days 1 to 15 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)

Pembrolizumab + COPDAC-28 (Group 2)

bleomycin DRUG

10 units/m\^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1)

Pembrolizumab + AVD (Group 1)

etoposide DRUG

125 mg/m\^2 IV on Days 1 to 5 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2)

Also known as: Etoposide Phosphate

Pembrolizumab + COPDAC-28 (Group 2)

Radiotherapy (RT) RADIATION

RT administered daily, dose dependent on randomization group and disease response.

Pembrolizumab + AVD (Group 1); Pembrolizumab + COPDAC-28 (Group 2)

pembrolizumab BIOLOGICAL

2 mg/kg intravenous (IV) up to a max of 200 mg (3 to 17 years of age) or 200 mg IV (18 to 25 years of age); cycle frequency Q3W

Also known as: MK-3475

Pembrolizumab + AVD (Group 1); Pembrolizumab + COPDAC-28 (Group 2)

cyclophosphamide DRUG

500 mg/m\^2 IV on days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)

Pembrolizumab + COPDAC-28 (Group 2)

Eligibility Criteria

• Age: 3 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (93)

Children's Hospital of Alabama ( Site 0023)

Birmingham, Alabama, 35233, United States

Location

Phoenix Childrens Hospital ( Site 0034)

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital ( Site 0046)

Little Rock, Arkansas, 72202, United States

Location

Kaiser - Orange County ( Site 0084)

Anaheim, California, 92806, United States

Location

Kaiser Permanente ( Site 0082)

Downey, California, 90242, United States

Location

Kaiser - Fontana ( Site 0083)

Fontana, California, 92335, United States

Location

MemorialCare Health System - Long Beach Medical Center-Cherese Mari Laulhere Children's Village ( Si

Long Beach, California, 90806, United States

Location

Kaiser Permanente Downey Medical Center ( Site 0024)

Los Angeles, California, 90027, United States

Location

Kaiser Permanente - Oakland ( Site 0047)

Oakland, California, 94611, United States

Location

Kaiser Permanente - Roseville ( Site 0080)

Roseville, California, 95661, United States

Location

Kaiser Permanente - Santa Clara ( Site 0079)

Santa Clara, California, 95051, United States

Location

Children's Hospital - Colorado ( Site 0028)

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center ( Site 0045)

Hartford, Connecticut, 06106, United States

Location

Yale Cancer Center ( Site 0061)

New Haven, Connecticut, 06510, United States

Location

Children's National Medical Center ( Site 0090)

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida ( Site 0051)

Gainesville, Florida, 32610, United States

Location

Memorial Regional Hospital/Joe DiMaggio Children's Hospital ( Site 0048)

Hollywood, Florida, 33021, United States

Location

Arnold Palmer Hospital ( Site 0065)

Orlando, Florida, 32806, United States

Location

Children's Healthcare of Atlanta at Egleston ( Site 0033)

Atlanta, Georgia, 30322, United States

Location

University of Chicago ( Site 0066)

Chicago, Illinois, 60637, United States

Location

Riley Hospital for Children ( Site 0091)

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Markey Cancer Center ( Site 0057)

Lexington, Kentucky, 40536-0293, United States

Location

University of Louisville-Norton Children's Hospital ( Site 0059)

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins University ( Site 0025)

Baltimore, Maryland, 21287, United States

Location

Children's Hospital of Michigan ( Site 0056)

Detroit, Michigan, 48201, United States

Location

Karmanos Cancer Institute ( Site 0002)

Detroit, Michigan, 48201, United States

Location

Children's Hospitals and Clinics of Minnesota ( Site 0036)

Minneapolis, Minnesota, 55404, United States

Location

St. Louis Children's Hospital ( Site 0038)

St Louis, Missouri, 63110, United States

Location

Alliance for Childhood Diseases ( Site 0064)

Las Vegas, Nevada, 89135, United States

Location

Hackensack University Medical Center ( Site 0026)

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey ( Site 0027)

New Brunswick, New Jersey, 08901, United States

Location

Roswell Park Cancer Institute ( Site 0040)

Buffalo, New York, 14263, United States

Location

Cohen Children's Medical Center of New York ( Site 0052)

New Hyde Park, New York, 11040, United States

Location

Columbia University/Herbert Irving Cancer Center ( Site 0063)

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center ( Site 0060)

New York, New York, 10065, United States

Location

Weill Cornell Medicine ( Site 0032)

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer ( Site 0044)

Chapel Hill, North Carolina, 27514, United States

Location

Cincinnati Children's Hospital Medical Center ( Site 0035)

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital ( Site 0037)

Columbus, Ohio, 43205-2696, United States

Location

St. Francis Hospital Cancer Center ( Site 0001)

Greenville, South Carolina, 29607, United States

Location

Vanderbilt University Medical Center-Ingram Cancer Center ( Site 0054)

Nashville, Tennessee, 37232, United States

Location

Dell Children's Medical Center Of Central Texas ( Site 0058)

Austin, Texas, 78723, United States

Location

Children's Medical Center ( Site 0030)

Dallas, Texas, 75235, United States

Location

Texas Children's Hospital ( Site 0042)

Houston, Texas, 77030, United States

Location

Methodist HealthCare System of San Antonio Clinical Trials Office, Texas Transplant Institute ( Site

San Antonio, Texas, 78229, United States

Location

Inova Fairfax Hospital ( Site 0031)

Falls Church, Virginia, 22042, United States

Location

Seattle Childrens Hospital ( Site 0022)

Seattle, Washington, 98105, United States

Location

Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 0507)

Curitiba, Paraná, 81520-060, Brazil

Location

Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0510)

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0500)

São Paulo, 04023-062, Brazil

Location

Hospital Pablo Tobon Uribe-Hematology ( Site 0565)

Medellín, Antioquia, 05034, Colombia

Location

Organizacion Clinica Bonnadona-Prevenir S.A.S. ( Site 0529)

Barranquilla, Atlántico, 080020, Colombia

Location

Instituto Nacional De Cancerologia ( Site 0566)

Bogotá, Bogota D.C., 111511, Colombia

Location

Oncomédica S.A.S ( Site 0527)

Montería, Departamento de Córdoba, 230001, Colombia

Location

Fakultni nemocnice v Motole ( Site 0356)

Prague, 150 06, Czechia

Location

Institut d'Hematologie-Oncologie Pediatrique (IHOP) ( Site 0448)

Lyon, Auvergne-Rhône-Alpes, 69008, France

Location

CHU de Marseille Hopital de la Timone Enfants ( Site 0449)

Marseille, Bouches-du-Rhone, 13005, France

Location

CHU de Bordeaux. Hopital Pellegrin ( Site 0447)

Bordeaux, Gironde, 33000, France

Location

Hôpital Jeanne de Flandre ( Site 0450)

Lille, Nord, 59037, France

Location

Institut Gustave Roussy ( Site 0445)

Villejuif, Val-de-Marne, 94800, France

Location

Hopital d'Enfants Armand Trousseau ( Site 0443)

Paris, 75012, France

Location

Hopital Universitaire Robert Debre ( Site 0446)

Paris, 75019, France

Location

Klinikum der Universitaet Muenchen-Campus Innenstadt ( Site 0414)

Munich, Bavaria, 80337, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH ( Site 0411)

Giessen, Hesse, 35392, Germany

Location

Universitaetsklinikum Essen ( Site 0415)

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Sit

Münster, North Rhine-Westphalia, 48149, Germany

Location

Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 0413)

Berlin, 13353, Germany

Location

Athens Childrens Hospital Aglaia Kyriakou ( Site 0361)

Athens, Attica, 115 27, Greece

Location

University of Athens - Aghia Sophia Childrens Hospital ( Site 0362)

Athens, Attica, 115 27, Greece

Location

University General Hospital of Thessaloniki "AHEPA" ( Site 0363)

Thessaloniki, Central Macedonia, 546 36, Greece

Location

Oncomedica ( Site 0545)

Guatemala City, 01010, Guatemala

Location

Unidad Nacional de Oncologia Pediatrica ( Site 0542)

Guatemala City, 01011, Guatemala

Location

Medi-K Cayala ( Site 0544)

Guatemala City, 01016, Guatemala

Location

Universita degli Studi di Roma La Sapienza ( Site 0403)

Roma, Abruzzo, 00161, Italy

Location

Centro di Riferimento Oncologico CRO ( Site 0404)

Aviano, Pordenone, 33081, Italy

Location

Azienda Ospedaliera Santobono - Pausilipon ( Site 0402)

Naples, 80123, Italy

Location

IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0400)

Roma, 00165, Italy

Location

Ospedale Infantile Regina Margherita ( Site 0401)

Torino, 10126, Italy

Location

Hospital Infantil de Mexico Federico Gomez ( Site 0535)

Mexico City, Mexico City, 06720, Mexico

Location

Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0531)

Monterrey, Nuevo León, 64460, Mexico

Location

UMAE Hospital de Especialidades - CMN La Raza ( Site 0536)

Azcapotzalco, 02990, Mexico

Location

Hematologica Alta Especialidad ( Site 0532)

Huixquilucan, 52787, Mexico

Location

Prinses Maxima Centrum ( Site 0461)

Utrecht, 3584 CS, Netherlands

Location

Narodny ustav detskych chorob ( Site 0372)

Bratislava, Bratislava Region, 833 40, Slovakia

Location

Wits Clinical Research ( Site 0323)

Johannesburg, Gauteng, 2193, South Africa

Location

Albert Alberts Stem Cell Transplant Centre ( Site 0324)

Pretoria, Gauteng, 0044, South Africa

Location

Wits Clinical Research ( Site 0321)

Soweto, Gauteng, 2193, South Africa

Location

Severance Hospital Yonsei University Health System ( Site 0221)

Seoul, 03722, South Korea

Location

Samsung Medical Center ( Site 0222)

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d Hebron ( Site 0432)

Barcelona, 08035, Spain

Location

Hospital Infantil Universitario Nino Jesus ( Site 0433)

Madrid, 28009, Spain

Location

Hospital Universitario La Paz ( Site 0434)

Madrid, 28046, Spain

Location

University College London Hospitals NHS Foundation Trust ( Site 0454)

London, London, City of, NW1 2PG, United Kingdom

Location

Related Publications (1)

• Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.

  PMID: 37505794 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hodgkin Disease

Interventions

pembrolizumab; Doxorubicin; Vinblastine; Dacarbazine; Cyclophosphamide; Vincristine; Prednisone; Prednisolone; Bleomycin; Etoposide; etoposide phosphate; Radiotherapy

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Therapeutics

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2018
• First Posted: January 23, 2018
• Study Start: April 9, 2018
• Primary Completion (Estimated): November 6, 2026
• Study Completion (Estimated): November 6, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CZ (1); NL (1); CO (4); IT (5); BR (3); ZA (3); US (47); KR (2); GB (1); DE (5); FR (7); ME (4); SL (1); GR (3); ES (3); GU (3)