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    The EU Clinical Trials Register currently displays   37192   clinical trials with a EudraCT protocol, of which   6121   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2016-001211-21
    Sponsor's Protocol Code Number:HO136
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-04-03
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2016-001211-21
    A.3Full title of the trial
    Phase I-II study combining Brentuximab Vedotin with second line salvage chemotherapy (R-DHAP) in CD30 positive diffuse large B-cell lymphoma patients refractory to first line chemotherapy or in first relapse who are eligible for high dose treatment followed by autologous stem cell transplantation
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase I-II study combining Brentuximab Vedotin with second line salvage chemotherapy (R-DHAP) in CD30 positive diffuse large B-cell lymphoma patients refractory to first line chemotherapy or in first relapse who are eligible for high dose treatment followed by autologous stem cell transplantation.
    Transplant BRaVE NHL
    Transplant BRaVE NHL: een fase I-II onderzoek, waarbij Brentuximab Vedotin in combinatie met tweedelijns chemotherapie (R-DHAP) wordt onderzocht bij patiënten met een CD30 positief diffuus grootcellig B-cel lymfoom die niet op de eerstelijns chemotherapie hebben gereageerd, of die een eerste recidief hebben ontwikkeld en die fit genoeg zijn om hoge dosis chemotherapie te ondergaan gevolgd door een autologe stamceltransplantatie.
    A.4.1Sponsor's protocol code numberHO136
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorHOVON Foundation
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportTakeda Oncology
    B.4.2CountryUnited States
    B.4.1Name of organisation providing supportDutch Cancer Society
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHOVON
    B.5.2Functional name of contact pointHOVON Data Center
    B.5.3 Address:
    B.5.3.1Street Address's Gravendijkwal 230
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015 CE
    B.5.3.4CountryNetherlands
    B.5.6E-mailhdc@erasmusmc.nl
    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.2.1.1.1Trade name Adcetris
    D.2.1.1.2Name of the Marketing Authorisation holderTakeda Pharma
    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.3.1Product namebrentuximab vedotin
    D.3.4Pharmaceutical form Powder for concentrate for 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.3.8INN - Proposed INNBRENTUXIMAB VEDOTIN
    D.3.9.1CAS number 914088-09-8
    D.3.9.3Other descriptive nameBRENTUXIMAB VEDOTIN
    D.3.9.4EV Substance CodeSUB32397
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee 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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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
    CD30 positive diffuse large B-cell lymphoma
    E.1.1.1Medical condition in easily understood language
    CD30 positive diffuse large B-cell lymphoma patients refractory to first line chemotherapy or in first relapse
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10012818
    E.1.2Term Diffuse large B-cell lymphoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 1 part
    - To identify the feasibility and RDL (recommended dose level) of brentuximab vedotin in combination with R-DHAP
    Phase 2 part
    - To evaluate the efficacy of the combination of brentuximab -vedotin and R-DHAP as salvage treatment in relapse/refractory DLBCL patients in terms of metabolic CR rate after the third cycle
    - To establish the rate of CTCAE grade 3/4 non-hematological toxicity, including neurotoxicity after each cycle of brentuximab vedotin-R-DHAP
    E.2.2Secondary objectives of the trial
    Phase 1 part
    - To assess the toxicity of brentuximab vedotin in combination with R-DHAP
    - To assess the success rate of autologous peripheral blood stem cell harvest after brentuximab vedotin-R-DHAP
    Phase 2 part
    -To asses the overall response rate (ORR) after 3 cycles and after ASCT
    -To assess the toxicity profile of brentuximab vedotin in combination with R-DHAP
    -To assess hematological recovery after each cycle of brentuximab vedotin-R-DHAP
    -To assess the success rate of harvesting an autologous peripheral blood stem cell graft
    -To assess the fraction of patients (CR/PR) eligible for ASCT who actually undergo ASCT
    -To assess peripheral blood neutrophil and platelet recovery after ASCT
    -To evaluate the progression free survival (PFS), event free survival (EFS), and overall survival (OS)
    -To identify predictive factors for response, PFS, EFS and OS (exploratory analysis)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • CD30 positive DLBCL, i.e. more than 1% of DLBCL cells CD30 positive (central pathology review results not required to enter patient into the study), according to the WHO classification 2008:
    - CD30 positive DLBCL, including EBV positive DLBCL
    - CD30 positive primary mediastinal B-cell lymphoma
    • Primary refractory to or in first relapse after first line therapy with R-CHOP or R-CHOP-like therapy (A rituximab biosimilar is permitted when it is registered for the indication of DLBCL)
    • Age ≥ 18 years (upper age limit for ASCT at the discretion of the participating center)
    • Measurable disease: on CT scan at least 1 lesion/node with a long axis of > 1.5 cm and at least one positive lesion on 18F-FDG PET scan
    • WHO performance status 0-2 (see appendix C)
    • Adequate hepatic function
    • Adequate renal function
    • Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5x10E9/L and platelet
    count ≥ 100 x 10E9/L
    • Hemoglobin must be ≥ 8 g/dL (5.0 mmol/L), transfusion is allowed
    • Eligible for high-dose chemotherapy and ASCT
    • Resolution of relevant toxicities from first-line therapy
    • Life expectancy of > 3 months with treatment
    • Negative pregnancy test at study entry, if applicable
    • Female patient is either post-menopausal for at least 1 year before screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, or agrees to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months after the last dose of study drug
    • Male patients, even if surgically sterilized, (i.e. status post vasectomy) agree to practice effective barrier contraception, or agrees to completely abstain from heterosexual intercourse, during the entire study period and through 12 months after the last dose of study drug
    • Written informed consent
    • Patient is capable of giving informed consent
    E.4Principal exclusion criteria
    • Peripheral sensory or motor neuropathy grade ≥ 2
    • Known cerebral or meningeal disease (NHL or any other etiology), including signs and symptoms of progressive multifocal leukoencephalopathy (PML)
    • Symptomatic neurological disease compromising normal activities of daily living or requiring medications
    • Transformed lymphoma
    • DLBCL after organ transplantation
    • Immunodeficiency-associated B-cell lymphoproliferative disease
    • Use of other investigational agents within at least 5 half-lives of the most recent agent used prior to study entry
    • Treatment with myelosuppressive chemotherapy or biological therapy ≤ 4 weeks before study entry
    • Female patients who are breast feeding
    • History of another malignancy less than 3 years before study inclusion, or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix
    • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin
    • Active hepatitis B or C infection as defined by positive serology and transaminitis. Non-active hepatitis B carriers or anti-HBc positive patients may be included if protected with lamuvidine or entecavir
    • HIV positivity
    • Radiation therapy within 8 weeks prior to start of protocol treatment. Emergency radiation therapy is allowed, as long as measurable disease (at non-irradiated sites) persists
    • Patients with a serious psychiatric disorder that could, in the investigator's opinion, potentially interfere with the completion of treatment according to protocol
    • Major organ dysfunction, unless NHL-related
    • Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study
    • Thyroid abnormalities when thyroid function cannot be maintained in the normal range by medication
    • Current participation in another clinical trial interfering with this trial
    • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
    • Claustrophobia to the extent that PET-CT is impossible
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1 part
    • The rate of patients with serious toxicity during cycle 1-2 of the combination BV-R-DHAP
    Phase 2 part
    Primary efficacy endpoint
    • Metabolic CR rate (PET-diagnostic CT) after the third cycle of BV-R-DHAP salvage therapy

    Primary feasibility/toxicity endpoints
    • Rate of grade 3/4 non-hematological toxicity, including neurotoxicity after each cycle of BV-R-DHAP
    E.5.1.1Timepoint(s) of evaluation of this end point
    Phase 1 part:
    The patients will be monitored closely for adverse events. The number of patients with serious toxicities (ST) will be determined at day 21 after start of cycle 1 or 2 , when 6 patients have been entered in a dose level.

    Phase 2 part: the endpoints will be evaluated when data for 3 BV-R-DHAP cycles are available for all patients
    E.5.2Secondary end point(s)
    Phase 1 part
    - (Serious) Adverse Events during combination treatment
    - Time to hematological recovery after each cycle of BV-R-DHAP
    - Time to recovery from non-hematological toxicity after each cycle of BV-R-DHAP
    - Administration of treatment: dose reductions, interval between cycles, discontinuation rate
    - Rate of successful PBSC collection (≥ 2x106 CD34+ cells/kg) after the third cycle of BV-R-DHAP

    Phase 2 part
    Secondary efficacy endpoints
    - Overall response rate (PR + CR) after the third cycle of BV-R-DHAP salvage therapy (based on the results of the FDG-PET/CT scan)
    - Overall response rate (PR + CR) after ASCT (based on the results of the FDG-PET/CT scan)
    - Metabolic CR rate (PET-CT) after ASCT
    - Fraction of patients (CR/PR) eligible for ASCT who actually undergo ASCT
    - Progression free survival (PFS), Event free survival (EFS), Overall survival (OS

    Secondary feasibility/toxicity endpoints
    - (Serious) Adverse Events during the combination treatment
    - Time to hematological recovery after each cycle of BV + R-DHAP
    - Administration of treatment: dose reductions, interval between courses, discontinuation rate
    - Rate of successful PBSC collection (≥ 2 x106 CD34+ cells/kg) after the second or third cycle of BV-R-DHAP
    - Time to hematological recovery after ASCT
    - (Serious) Adverse Events after ASCT
    E.5.2.1Timepoint(s) of evaluation of this end point
    Phase 1 part
    These endpoints will be evaluated when the relevant data for all patients are available in the phase 1
    Phase 2 part
    These endpoints will be evaluated when the relevant data for all patients are available
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    dose finding
    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 No
    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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 38
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 5
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 43
    F.4.2.2In the whole clinical trial 43
    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)
    None
    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 HOVON Foundation
    G.4.3.4Network Country Netherlands
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-04-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-04-12
    P. End of Trial
    P.End of Trial StatusOngoing
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