Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43387   clinical trials with a EudraCT protocol, of which   7179   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools

    < Back to search results

    Print Download

    EudraCT Number:2017-001123-53
    Sponsor's Protocol Code Number:MK-3475-667
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-08-25
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2017-001123-53
    A.3Full title of the trial
    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).
    Odslepené, nekontrolované, multicentrické hodnotenie II. fázy s MK-3475 (pembrolizumab) u detí a mladých dospelých s novo diagnostikovaným klasickým Hodgkinovým lymfómom s nedostatočnou (pomalou včasnou) odpoveďou na prvolíniovú chemoterapiu (hodnotenie KEYNOTE 667)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II trial of MK-3475 (pembrolizumab) in children and young adults with classical Hodgkin lymphoma
    Hodnotenie II. fázy s MK-3475 (pembrolizumab) u detí a mladých dospelých s klasickým Hodgkinovým lymfómom
    A.4.1Sponsor's protocol code numberMK-3475-667
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03407144
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/008/2018
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck Sharp & Dohme LLC
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck Sharp & Dohme LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme LLC
    B.5.2Functional name of contact pointGlobal Clinical Trial Operations
    B.5.3 Address:
    B.5.3.1Street Address126 East Lincoln Avenue P.O. Box 2000
    B.5.3.2Town/ cityRahway, NJ
    B.5.3.3Post code07065
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1732594 5269
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D. name KEYTRUDA (pembrolizumab, MK-3475)
    D. of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    cHL in children and young adults
    E.1.1.1Medical condition in easily understood language
    Classical Hodgkin lymphoma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10080208
    E.1.2Term Classical Hodgkin lymphoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the objective response rate (ORR) by International Working Group (IWG) criteria as assessed by blinded independent central review (BICR) [Cheson, B. D., et al 2007] of pembrolizumab in combination with chemotherapy in slow early responders (SERs) by risk group (low, high).

    E.2.2Secondary objectives of the trial
    1.To evaluate the rate of Positron Emission Tomography (PET) negativity, 2-year event-free survival (EFS) after study enrollment by IWG criteria as assessed by BICR, and overall survival (OS) of pembrolizumab in combination with chemotherapy in SERs by risk group
    2.To evaluate the exposure to radiation therapy (RT) and its associated toxicity in SERs by risk group
    3.To evaluate the rate of PET negativity per investigator assessment in Group 1 participants after completing 2 cycles of ABVD induction
    4.To evaluate the 3-year EFS and OS in rapid early responders (RERs) by risk group
    5.To evaluate serum TARC as a potential biomarker in SERs by risk group
    6.To evaluate the safety of pembrolizumab in combination with chemotherapy in SERs by risk group
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Must be male or female between the ages of 3 and 25 years inclusive on the day of signing informed consent/assent
    2. Group 1: Must have newly diagnosed, pathologically confirmed cHL at Stages IA, IB and IIA without bulky disease defined as the presence of any of the following:
    - Nodal area >6cm OR
    - Mass/thoracic diameter >one-third
    Group 2: Must have newly diagnosed, pathologically confirmed cHL at Stages IIEB, IIIEA, IIIEB, IIIB, IVA and IVB
    3. Must have measurable disease per investigator assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Measurable disease is defined as the existence of at least one measurable nodal lesion present, defined as a lymph node or nodal mass that is either >15 mm in longest diameter or >10 mm in short axis on anatomic imaging (ie, a diagnostic CT or MRI) and appropriate for reproducible measurements. A lesion that appears measurable, but is located in an area that was previously irradiated, can be considered measurable if it has shown growth since the completion of radiation
    4.Male participants are eligible to participate if they agree to the following during the
    interv period and for at least the time needed to eliminate each study interv after the last dose of study interv. The length of time required to continue contracep for each study intervention is:
    - Pembrolizumab: no contraception requir
    - Chemotherapy: refrain from donating sperm for 90 days after last dose of chemother
    PLUS either:
    - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent
    - Uses contraception unless confirmed to be azoospermic documented from the site personnel’s review of the participant’s medical records, medical examination,
    or medical history interview as detailed below:
    o uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
    o Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    5. female participant is eligible to participate if she is not pregnant , not breastfeeding, and at least one of the following conditions applies:
    - Not a woman of childbearing potential (WOCBP)
    - Is a WOCBP and uses contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention 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. The length of time
    required to continue contraception for each study intervention is as follows:
    o Vinblastine and Vincristine: 30 days
    o Other Chemotherapies: 180 days
    o Pembrolizumab: 120 days. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
    Contraceptive use by women should be consistent with local
    regulations regarding the methods of contraception for those participating in clinical
    studies. If the contraception requirements in the local label for any of the study
    interventions is more stringent than the requirements above, the local label
    requirements are to be followed.
    - has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study
    intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
    Abstains from breastfeeding during the study at least 120 days after study intervention for
    pembrolizumab and 180 days for chemotherapy, whichever is last.
    Has had her medical history, menstrual history, and recent sexual activity reviewed
    by the investigator to decrease the risk for inclusion of a woman with an early
    undetected pregnancy
    6. The participant (or legally acceptable representative if applicable) provides documented informed consent/assent for the study. The participant may also provide consent/assent for FBR. However the participant may participate in the main study without participating in FBR
    7. Must have a performance status as defined below:
    - Lansky Play-Performance Scale ≥50 for children up to 16 years of age
    - Karnofsky score ≥50 for participants ≥16 years of age
    8. Must have adequate organ function
    E.4Principal exclusion criteria
    1. Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Participants who have had allogeneic hematopoietic stem cell transplant greater than 5 years ago are eligible as long as there are no symptoms of graft-versus-host disease (GVHD)
    2. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
    3. Baseline left ventricular ejection fraction value <50% or shortening fraction of <27%
    4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (ie, CTLA-4, OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK-3475) clinical study
    5. Received prior systemic anti-cancer therapy, including investigational agent
    6.Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed
    7. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
    8. Has a diagnosis of lymphocyte-predominant HL
    9. Has a diagnosis of immunodeficiency or is expected to be receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab. The use of physiologic doses of corticosteroids (up to 5 mg/m2/day prednisone equivalent) may be approved after consultation with the Sponsor
    10. Has a known additional malignancy that is progressing or requires active treatment within the past 3 years

    11. Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator at the time of diagnosis
    12. Has severe hypersensitivity (≥Grade 3) to any study therapies including any excipients
    13. An active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
    14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
    15. Has an active infection requiring systemic therapy
    16. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
    17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
    18. 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
    19. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
    20. Participants who have not adequately recovered from major surgery or have ongoing
    surgical complications.
    E.5 End points
    E.5.1Primary end point(s)
    Objective Response Rate (ORR) in SER Participants By Risk Group (Low, High) as Assessed by Blinded Independent Central Review (BICR)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 5 years
    E.5.2Secondary end point(s)
    1.Rate of Positron Emission Tomography (PET) Scan Negativity in SER Participants By Risk Group (Low, High) After AVD or COPDAC-28 Chemotherapy
    2.Event-Free Survival (EFS) in SER Participants By Risk Group (Low, High) as Assessed by BICR
    3.Overall Survival (OS) in SER Participants By Risk Group (Low, High)
    4.Exposure to Radiotherapy (RT) in SER Participants By Risk Group (Low, High)
    5.Rate of PET Scan Negativity In Group 1 Participants After ABVD Induction Therapy
    6.EFS in Rapid Early Responder (RER) Participants By Risk Group (Low, High) as Assessed by Investigator
    7.OS in RER Participants By Risk Group (Low, High)
    8.Serum Thymus and Activation-Regulated Chemokine (TARC) Levels in SER Participants By Risk Group (Low, High)
    9.Number of SER Participants Experiencing an Adverse Event (AE) By Risk Group (Low, High)
    10.Number of SER Participants Discontinuing Study Treatment Due to AEs By Risk Group (Low, High)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.Up to 5 years
    2.Up to 5 years
    3.Up to 5 years
    4.Up to 5 years
    5.Up to 5 years
    6.Up to 5 years
    7.Up to 5 years
    8.Up to 5 years
    9.Up to 5 years
    10.Up to 5 years
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA31
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Korea, Republic of
    New Zealand
    South Africa
    United States
    Russian Federation
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 340
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F. of subjects for this age range: 17
    F.1.1.6Adolescents (12-17 years) Yes
    F. of subjects for this age range: 266
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 57
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 255
    F.4.2.2In the whole clinical trial 340
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation European Network-Paediatric Hodgkin’s Lymphoma Study Group (EuroNet-PHL)
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-12-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-09-20
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands