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   43865   clinical trials with a EudraCT protocol, of which   7286   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

    Summary
    EudraCT Number:2019-000842-36
    Sponsor's Protocol Code Number:Version128May2019
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-11-22
    Trial results View 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 ConcernedUK - MHRA
    A.2EudraCT number2019-000842-36
    A.3Full title of the trial
    A Polatuzumab Vedotin Containing Chemo-Immunotherapeutic Regimen in Patients with Diffuse Large B-Cell Lymphoma Unsuitable for Full Dose R-CHOP Therapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Polatuzumab vedotin combined with standard chemo-immunotherapy drugs in diffuse large B-cell lymphoma
    A.3.2Name or abbreviated title of the trial where available
    APOLLO
    A.4.1Sponsor's protocol code numberVersion128May2019
    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 SponsorThe Clatterbridge Cancer Centre NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    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 supportRoche Products Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Liverpool
    B.5.2Functional name of contact pointCRUK Liverpool Cancer Trials Unit
    B.5.3 Address:
    B.5.3.1Street Address1st Floor Block C, Waterhouse Building, 3 Brownlow Street
    B.5.3.2Town/ cityLiverpool
    B.5.3.3Post codeL69 3GL
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01517948383
    B.5.5Fax number01517948931
    B.5.6E-mailr.dagnall@liverpool.ac.uk
    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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2013
    D.3 Description of the IMP
    D.3.1Product namePolatuzumab Vedotin
    D.3.4Pharmaceutical form Lyophilisate 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 INNPolatuzumab Vedotin
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Diffuse large B-cell lymphoma in patients with co-morbidities who cannot tolerate full dose R-CHOP.
    E.1.1.1Medical condition in easily understood language
    A cancer of the blood affecting B-cells.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    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
    The primary objective is to determine if the efficacy of polatuzumab vedotin, rituximab, gemcitabine and prednisolone (POLA-R-GCP) or polatuzumab vedotin, rituximab, doxorubicin, cyclophosphamide and prednisolone (POLA-R-mini-CHP) is sufficient for further investigation in patients not fit for full dose R-CHOP chemo-immunotherapy.
    E.2.2Secondary objectives of the trial
    The secondary research objective is to assess the safety and tolerability of POLA-R-GCP or POLA-R-mini-CHP through an analysis of the frequency of adverse events (AEs) and the number of patients who discontinue therapy due to toxicity.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Males and female subjects ≥16 years of age at the time of enrolment
    -Ability to understand and sign written informed consent
    -Adequate contraceptive precautions if relevant.
    -No active malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix in the last 3 years.
    -ECOG performance status 0-2, at the time of screening.
    -Measurable disease
    -Previously untreated histologically proven CD20 and CD79b +ve Diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) according to the current World Health Organisation 2016 classification including all morphological variants.
    o DLBCL, not otherwise specified (NOS) including GCB and ABC
    o T-cell / histiocyte rich large B lymphoma
    o Epstein Barr virus positive DLBCL NOS
    o ALK –positive large B cell lymphoma
    o HHV8 positive DLBCL, NOS
    o High grade B –cell lymphoma with MYC and BCL2 and / or BCL6 rearrangements (double hit or triple hit lymphoma)
    o High grade B cell lymphoma, NOS
    -The B-cell nature of the proliferation must be verified by the positivity with anti-CD20 and anti-CD79b antibodies before entry to the study. A central pathology panel will review all histology.
    -At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT or MRI
    -Availability of archival or freshly obtained tumour tissue
    -No previous chemotherapy, radiotherapy, or other investigational drug for this indication.
    -Patients with a cardiac status that does not allow the administration of 6 courses of R-CHOP as defined by an ejection fraction of ≤ 50% either assessed by echocardiography or nuclear medicine examination [MUGA] or New York Heart Association classification Grade III or IV.
    If the ejection fraction is >50% but there is evidence of other significant co-morbid cardiac risk factors (i.e. Hypertension, Diabetes Mellitus, previous history of Ischaemic heart disease, previous cardiac dysfunction, renal impairment etc.) that may preclude full dose anthracycline use, these patients may be considered for trial entry.
    -Adequate bone marrow function as defined by:
    Platelets > 100x109 /l; WBC > 3 x 109 /l; Neutrophils > 1.0 x 109 /l at the time of study entry - unless attributed to bone marrow infiltration by lymphoma.
    Serum bilirubin < 50 mol/l and transaminases < 2.5 upper limit of institutional normal range unless elevated levels attributed to lymphoma.
    Glomerular filtration rate >30ml/minute as assessed by urinary creatinine clearance or Cockcroft-Gault Formula.
    -No concurrent uncontrolled medical condition
    -Life expectancy > 3 months.
    -Bulky stage IA (defined as lymph node or lymph node mass greater than 10cm in diameter), stage IB, stage II, stage III and stage IV.
    -Patients receiving corticosteroid treatment with ≤ 20mg /day of prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks` duration prior to the start of Cycle 1
    -If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of treatment, prednisolone 1 mg/kg or equivalent is permitted to a maximum of 14 days as a pre-phase treatment
    E.4Principal exclusion criteria
    a. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
    b. Patients with central nervous system or meningeal involvement by the lymphoma
    c. Contraindication to any of the individual components of mini-CHP or GCP including prior administration of anthracyclines.
    d. Prior organ transplantation
    e. Demyelinating Charcot-Marie-Tooth disease
    f. Burkitt lymphoma
    g. Primary Mediastinal B-cell Lymphoma
    h. Prior treatment with cytotoxic drugs within 5 years of screening for any condition (e.g. cancer, rheumatoid arthritis) or prior use of any anti-CD20 antibody.
    i. Patients with a previous diagnosis of low grade lymphoma (NB: a concurrent finding of low grade NHL in the BM at presentation is allowed) and patients with non-bulky stage IA disease
    j. Patients with positive serology for: HIV, HTVL-1, HCV, HepBcAb, HepBsAg
    k. Patients with suspected active Tuberculosis or latent Tuberculosis
    l. Pregnancy or lactation or intending to become pregnant during study
    m. Peripheral neuropathy > Grade 1
    n. Known active bacterial, viral, fungal or parasitic infections
    o. Illicit drug or alcohol abuse; active viral or other hepatitis or cirrhosis
    p. Prolonged corticosteroid use > 20mg/day of prednisolone or equivalent for purposes other than lymphoma symptom control
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome is the 12-month Progression Free Survival rate which is measured as a binary covariate. Progression-free survival is defined as disease progression or recurrence, or death from any cause, (defined as days from the date of cohort assignment to event)as assessed by the investigator using the revised Lugano response criteria for malignant lymphoma (2016).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Occurring within 12 months (from the date of cohort assignment).
    E.5.2Secondary end point(s)
    a. Toxicity: The frequency of Grade 3-4 adverse events (AEs) - Grade 3-4 toxicities occurring anytime from the start of treatment until 12 months following the last dose of treatment. Adverse events/Toxicities will be assessed according to standard National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 following each cycle of treatment and at each subsequent follow-up visit until 12 months after the last dose of treatment.
    b. The number of patients completing the 6 planned courses of therapy in each cohort
    c. Investigator assessed end-of-treatment FDG-PET Response as assessed by a PET/CT scan performed at the end of treatment using the revised Lugano response criteria for malignant lymphoma (2016).
    d. Overall survival measured as the time from recruitment until death by any cause
    e. Time to next treatment
    f. Quality of life
    g. Co-morbidity/Frailty assessment pre- and post-treatment (excluding haematological co-morbidities)
    E.5.2.1Timepoint(s) of evaluation of this end point
    a. Until 12 months after the last treatment dose
    b. N/A
    c. 4-6 weeks after last course of treatment
    d. 12 months from the date of cohort assignment
    e. From date of last treatment to next treatment over a maximum of 24 months
    f. Pre-treatment; 4-6 weeks after last course of treatment; every 3 months for 2 years, and then every 4 months for 1 year and then every 6 months for two years
    g. Pre-treatment and 4-6 weeks after last course of treatment
    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 No
    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) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other 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 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 concerned10
    E.8.5The trial involves multiple Member States No
    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
    The last visit of the last patient will define the end of trial. This will be followed by the completion of a study report.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 36
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state56
    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)
    Those patients with an anatomical response after 3 cycles will continue onto to receive a further 3 cycles of treatment.

    Patients may be withdrawn from trial treatment due to failure to respond, disease progression, unacceptable toxicity, physician choice or patient choice. For these patients, further treatment will be at the discretion of the local investigator in accordance with local practice.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-12-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-04-07
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    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-Mon Apr 29 17:19:49 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA