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

Primary Purpose

Hodgkin Lymphoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
pembrolizumab
doxorubicin
vinblastine
dacarbazine
cyclophosphamide
vincristine
prednisone/prednisolone
bleomycin
etoposide
Radiotherapy (RT)
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

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

3 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Experimental

Arm Label

Pembrolizumab + AVD (Group 1)

Pembrolizumab + COPDAC-28 (Group 2)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy
The rate of PET negativity for SER participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of AVD (Group 1) or four cycles of COPDAC-28 (Group 2), in combination with pembrolizumab. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. 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.
Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR
EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by BICR using IWG criteria.
Overall Survival (OS) in SER Participants By Risk Group (Low, High)
OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.
Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)
The frequency of RT received by eligible participants (positive PET response, i.e. Deauville score of 4 or 5) will be reported.
Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy
The rate of PET negativity for Group 1 participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of ABVD induction as per investigator assessment. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the FDG avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. 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.
EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator
EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by the investigator.
OS in RER Participants By Risk Group (Low, High)
OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.
Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High)
Serum TARC levels will be measured and evaluated as a potential biomarker in SER participants by risk group at screening, early, and late response assessments.
Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of SER participants who experience an AE will be reported for each arm.
Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of SER participants who discontinue study treatment due to an AE will be reported for each arm.

Full Information

First Posted
January 17, 2018
Last Updated
October 12, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03407144
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 9, 2018 (Actual)
Primary Completion Date
February 13, 2027 (Anticipated)
Study Completion Date
February 13, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
Keywords
Programmed Death-1 (PD-1), PD1, Programmed Death-Ligand 1 (PD-L1), PDL1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
340 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab + AVD (Group 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
Pembrolizumab + COPDAC-28 (Group 2)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
pembrolizumab
Other Intervention Name(s)
MK-3475
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
vinblastine
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
dacarbazine
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
500 mg/m^2 IV on days 1 and 8 as part of COPDAC-28 chemotherapy (cycle frequency: Q4W, Group 2)
Intervention Type
Drug
Intervention Name(s)
vincristine
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
prednisone/prednisolone
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
bleomycin
Intervention Description
10 units/m^2 IV on Days 1 and 15 as part of ABVD induction therapy (cycle frequency: Q4W, Group 1)
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
Etoposide Phosphate
Intervention Description
125 mg/m^2 IV on Days 1 to 5 as part of OEPA induction therapy (cycle frequency: Q4W, Group 2)
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy (RT)
Intervention Description
RT administered daily, dose dependent on randomization group and disease response.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as Assessed by Blinded Independent Central Review (BICR)
Description
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.
Time Frame
Up to approximately 8 years
Secondary Outcome Measure Information:
Title
Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy
Description
The rate of PET negativity for SER participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of AVD (Group 1) or four cycles of COPDAC-28 (Group 2), in combination with pembrolizumab. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. 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.
Time Frame
Up to approximately 8 years
Title
Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR
Description
EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by BICR using IWG criteria.
Time Frame
Up to approximately 8 years
Title
Overall Survival (OS) in SER Participants By Risk Group (Low, High)
Description
OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.
Time Frame
Up to approximately 8 years
Title
Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)
Description
The frequency of RT received by eligible participants (positive PET response, i.e. Deauville score of 4 or 5) will be reported.
Time Frame
Up to approximately 8 years
Title
Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy
Description
The rate of PET negativity for Group 1 participants is the percentage of participants with PET negativity (defined as Deauville score 1, 2 or 3) after two cycles of ABVD induction as per investigator assessment. The Deauville 5-point scoring system is an internationally accepted and utilized five-point scoring system for the FDG avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG PET scan: Score 1= No uptake above the background, Score 2= Uptake ≤ mediastinum, Score 3= Uptake > mediastinum but ≤ liver, Score 4= Uptake moderately increased compared to the liver at any site, Score 5= Uptake markedly increased compared to the liver at any site or new lesions, Score X= New areas of uptake unlikely to be related to lymphoma. 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.
Time Frame
Up to approximately 8 years
Title
EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator
Description
EFS is defined as the time from study enrollment to the first documented disease progression or recurrence, or death due to any cause, whichever occurs first. Progression/disease recurrence will be determined by the investigator.
Time Frame
Up to approximately 8 years
Title
OS in RER Participants By Risk Group (Low, High)
Description
OS is defined as the time from study enrollment to death due to any cause. Participants without documented death will be censored at the date of the last follow-up.
Time Frame
Up to approximately 8 years
Title
Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High)
Description
Serum TARC levels will be measured and evaluated as a potential biomarker in SER participants by risk group at screening, early, and late response assessments.
Time Frame
Up to approximately 8 years
Title
Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High)
Description
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of SER participants who experience an AE will be reported for each arm.
Time Frame
Up to approximately 8 years
Title
Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High)
Description
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. 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 treatment. The number of SER participants who discontinue study treatment due to an AE will be reported for each arm.
Time Frame
Up to approximately 8 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Alabama ( Site 0023)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Phoenix Childrens Hospital ( Site 0034)
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Arkansas Children's Hospital ( Site 0046)
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Kaiser - Orange County ( Site 0084)
City
Anaheim
State/Province
California
ZIP/Postal Code
92806
Country
United States
Facility Name
Kaiser Permanente ( Site 0082)
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
Kaiser - Fontana ( Site 0083)
City
Fontana
State/Province
California
ZIP/Postal Code
92335
Country
United States
Facility Name
MemorialCare Health System - Long Beach Medical Center-Cherese Mari Laulhere Children's Village ( Si
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Kaiser Permanente Downey Medical Center ( Site 0024)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Kaiser Permanente - Oakland ( Site 0047)
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Kaiser Permanente - Roseville ( Site 0080)
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Kaiser Permanente - Santa Clara ( Site 0079)
City
Santa Clara
State/Province
California
ZIP/Postal Code
95051
Country
United States
Facility Name
Children's Hospital - Colorado ( Site 0028)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Connecticut Children's Medical Center ( Site 0045)
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Yale Cancer Center ( Site 0061)
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Children's National Medical Center ( Site 0090)
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Florida ( Site 0051)
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Memorial Regional Hospital/Joe DiMaggio Children's Hospital ( Site 0048)
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Arnold Palmer Hospital ( Site 0065)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Children's Healthcare of Atlanta at Egleston ( Site 0033)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago ( Site 0066)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Riley Hospital for Children ( Site 0091)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kentucky Markey Cancer Center ( Site 0057)
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0293
Country
United States
Facility Name
University of Louisville-Norton Children's Hospital ( Site 0059)
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Johns Hopkins University ( Site 0025)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Children's Hospital of Michigan ( Site 0056)
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Karmanos Cancer Institute ( Site 0002)
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota ( Site 0036)
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
St. Louis Children's Hospital ( Site 0038)
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Alliance for Childhood Diseases ( Site 0064)
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
Hackensack University Medical Center ( Site 0026)
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey ( Site 0027)
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Roswell Park Cancer Institute ( Site 0040)
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Cohen Children's Medical Center of New York ( Site 0052)
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Columbia University/Herbert Irving Cancer Center ( Site 0063)
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center ( Site 0060)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill Cornell Medicine ( Site 0032)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer ( Site 0044)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center ( Site 0035)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital ( Site 0037)
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205-2696
Country
United States
Facility Name
St. Francis Hospital Cancer Center ( Site 0001)
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607
Country
United States
Facility Name
Vanderbilt University Medical Center-Ingram Cancer Center ( Site 0054)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Dell Children's Medical Center Of Central Texas ( Site 0058)
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
Children's Medical Center ( Site 0030)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Texas Children's Hospital ( Site 0042)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Methodist HealthCare System of San Antonio Clinical Trials Office, Texas Transplant Institute ( Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Inova Fairfax Hospital ( Site 0031)
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Seattle Childrens Hospital ( Site 0022)
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 0507)
City
Curitiba
State/Province
Parana
ZIP/Postal Code
81520-060
Country
Brazil
Facility Name
Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 0510)
City
Natal
State/Province
Rio Grande Do Norte
ZIP/Postal Code
59075-740
Country
Brazil
Facility Name
Instituto de Oncologia Pediatrica - GRAACC - Unifesp ( Site 0500)
City
Sao Paulo
ZIP/Postal Code
04023-062
Country
Brazil
Facility Name
Hospital Pablo Tobon Uribe-Hematology ( Site 0565)
City
Medellin
State/Province
Antioquia
ZIP/Postal Code
05034
Country
Colombia
Facility Name
Organizacion Clinica Bonnadona-Prevenir S.A.S. ( Site 0529)
City
Barranquilla
State/Province
Atlantico
ZIP/Postal Code
080020
Country
Colombia
Facility Name
Oncomédica S.A.S ( Site 0527)
City
Monteria
State/Province
Cordoba
ZIP/Postal Code
230001
Country
Colombia
Facility Name
Instituto Nacional De Cancerologia ( Site 0566)
City
Bogotá
State/Province
Distrito Capital De Bogota
ZIP/Postal Code
111511
Country
Colombia
Facility Name
Fakultni nemocnice v Motole ( Site 0356)
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
CHU de Marseille Hopital de la Timone Enfants ( Site 0449)
City
Marseille
State/Province
Bouches-du-Rhone
ZIP/Postal Code
13005
Country
France
Facility Name
CHU de Bordeaux. Hopital Pellegrin ( Site 0447)
City
Bordeaux
State/Province
Gironde
ZIP/Postal Code
33000
Country
France
Facility Name
Hôpital Jeanne de Flandre ( Site 0450)
City
Lille
State/Province
Nord
ZIP/Postal Code
59037
Country
France
Facility Name
Institut d'Hematologie-Oncologie Pediatrique (IHOP) ( Site 0448)
City
Lyon
State/Province
Rhone-Alpes
ZIP/Postal Code
69008
Country
France
Facility Name
Institut Gustave Roussy ( Site 0445)
City
Villejuif
State/Province
Val-de-Marne
ZIP/Postal Code
94800
Country
France
Facility Name
Hopital d'Enfants Armand Trousseau ( Site 0443)
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hopital Universitaire Robert Debre ( Site 0446)
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Klinikum der Universitaet Muenchen-Campus Innenstadt ( Site 0414)
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
80337
Country
Germany
Facility Name
Universitaetsklinikum Giessen und Marburg GmbH ( Site 0411)
City
Giessen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Universitaetsklinikum Essen ( Site 0415)
City
Essen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitätsklinikum Münster - Albert Schweitzer Campus-Pädiatrische Hämatologie und Onkologie ( Sit
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
Facility Name
Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 0413)
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Athens Childrens Hospital Aglaia Kyriakou ( Site 0361)
City
Athens
State/Province
Attiki
ZIP/Postal Code
115 27
Country
Greece
Facility Name
University of Athens - Aghia Sophia Childrens Hospital ( Site 0362)
City
Athens
State/Province
Attiki
ZIP/Postal Code
115 27
Country
Greece
Facility Name
University General Hospital of Thessaloniki "AHEPA" ( Site 0363)
City
Thessaloniki
State/Province
Kentriki Makedonia
ZIP/Postal Code
546 36
Country
Greece
Facility Name
Oncomedica ( Site 0545)
City
Guatemala
ZIP/Postal Code
01010
Country
Guatemala
Facility Name
Unidad Nacional de Oncologia Pediatrica ( Site 0542)
City
Guatemala
ZIP/Postal Code
01011
Country
Guatemala
Facility Name
Medi-K Cayala ( Site 0544)
City
Guatemala
ZIP/Postal Code
01016
Country
Guatemala
Facility Name
Universita degli Studi di Roma La Sapienza ( Site 0403)
City
Roma
State/Province
Abruzzo
ZIP/Postal Code
00161
Country
Italy
Facility Name
Centro di Riferimento Oncologico CRO ( Site 0404)
City
Aviano
State/Province
Pordenone
ZIP/Postal Code
33081
Country
Italy
Facility Name
Azienda Ospedaliera Santobono - Pausilipon ( Site 0402)
City
Napoli
ZIP/Postal Code
80123
Country
Italy
Facility Name
IRCCS Ospedale Pediatrico Bambino Gesu ( Site 0400)
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Ospedale Infantile Regina Margherita ( Site 0401)
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Severance Hospital Yonsei University Health System ( Site 0221)
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Samsung Medical Center ( Site 0222)
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Hospital Infantil de Mexico Federico Gomez ( Site 0535)
City
Mexico D.F.
State/Province
Distrito Federal
ZIP/Postal Code
06720
Country
Mexico
Facility Name
Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0531)
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Facility Name
UMAE Hospital de Especialidades - CMN La Raza ( Site 0536)
City
Azcapotzalco
ZIP/Postal Code
02990
Country
Mexico
Facility Name
Hematologica Alta Especialidad ( Site 0532)
City
Huixquilucan
ZIP/Postal Code
52787
Country
Mexico
Facility Name
Prinses Maxima Centrum ( Site 0461)
City
Utrecht
ZIP/Postal Code
3584 CS
Country
Netherlands
Facility Name
Narodny ustav detskych chorob ( Site 0372)
City
Bratislava
State/Province
Bratislavsky Kraj
ZIP/Postal Code
833 40
Country
Slovakia
Facility Name
Wits Clinical Research ( Site 0323)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Albert Alberts Stem Cell Transplant Centre ( Site 0324)
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0044
Country
South Africa
Facility Name
Wits Clinical Research ( Site 0321)
City
Soweto
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Hospital Universitari Vall d Hebron ( Site 0432)
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Infantil Universitario Nino Jesus ( Site 0433)
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hospital Universitario La Paz ( Site 0434)
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
University College London Hospitals NHS Foundation Trust ( Site 0454)
City
London
State/Province
London, City Of
ZIP/Postal Code
NW1 2PG
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://merckclinicaltrials.com
Description
Merck Clinical Trials Information

Learn more about this trial

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

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