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   43857   clinical trials with a EudraCT protocol, of which   7284   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:2020-002142-17
    Sponsor's Protocol Code Number:CLL-Frail
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-07-26
    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 ConcernedAustria - BASG
    A.2EudraCT number2020-002142-17
    A.3Full title of the trial
    CLL-Frail – A prospective, multicenter phase II trial of acalabrutinib in very old (≥80y) or frail CLL-Patients
    CLL-Frail – Eine prospektive, multizentrische Phase II Studie mit Acalabrutinib bei sehr alten (≥80 Jahre) oder gebrechlichen Patienten mit chronischer lymphatischer Leukämie (CLL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of a treatment with acalabrutinib in very old (≥80 years) or frail patients with chronic lymphocytic leukemia
    Beurteilung einer Therapie mit Acalabrutinib bei sehr alten (≥80 Jahre) oder gebrechlichen Patienten mit chronischer lymphatischer Leukämie
    A.3.2Name or abbreviated title of the trial where available
    CLL-Frail
    A.4.1Sponsor's protocol code numberCLL-Frail
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04883749
    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 SponsorUniversity of Cologne
    B.1.3.4CountryGermany
    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 supportAstraZeneca
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGerman CLL Study Group
    B.5.2Functional name of contact pointInformation Desk
    B.5.3 Address:
    B.5.3.1Street AddressGleueler Str. 176 - 178
    B.5.3.2Town/ cityKöln
    B.5.3.3Post code50935
    B.5.3.4CountryGermany
    B.5.4Telephone number0049 221 47888220
    B.5.5Fax number0049 221 47886886
    B.5.6E-mailcll-frail@uk-koeln.de
    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 Calquence
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB, SE-151 85 Södertälje, Sweden
    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 nameAcalabrutinib/ ACP-196
    D.3.4Pharmaceutical form Capsule, hard + tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNACALABRUTINIB
    D.3.9.1CAS number 1420477-60-6
    D.3.9.3Other descriptive nameACP-196
    D.3.9.4EV Substance CodeSUB182073
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with CLL requiring treatment
    E.1.1.1Medical condition in easily understood language
    Patients with chronic lymphocytic leukaemia in need of treatment
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10008958
    E.1.2Term Chronic lymphocytic leukaemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this trial aims to show the efficacy of acalabrutinib in a cohort of CLL-patients ≥80 years or with a FRAIL scale score >2 via the patient’s own assessment.
    E.2.2Secondary objectives of the trial
    The secondary objective of this trial is to show the safety of acalabrutinib as well as feasibility of conducting a trial in this so far underrepresented patient group
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥80 years AND/OR considered too frail for intensive/standard treatment defined by a frailty score of >2 on the FRAIL-Scale via the patient´s assessment.
    2. Have documented CLL requiring treatment according to iwCLL 2018 criteria14.
    3. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
    4. GFR >30ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 – age) x body-weight)/ (72 x creatinine), for women x 0, 85) or an equally accurate method.
    a. Please note: Patients currently on hemodialysis are excluded from participating in the trial.
    5. Adequate liver function as indicated by a total bilirubin ≤ 3 x, AST/ ALT ≤ 3 x the institu-tional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syn-drome.
    6. Adequate marrow function independent of growth factor or transfusion support as fol-lows, unless cytopenia is due to marrow involvement of CLL:
    a. Absolute neutrophil count ≥ 1.0 × 10^9/L.
    b. Platelet counts ≥ 30 × 10^9/L; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 10^9/L if there is bone marrow involvement.
    c. Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to marrow involvement of CLL).
    7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month/every three months if persistently negative until 12 months after last month of treat-ment), negative testing for hepatitis C RNA within 6 weeks prior to registration.
    8. Life expectancy ≥ 3 months.
    9. Maximum of 1 previous treatment for CLL.
    10. In case of a recent previous treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL-Frail trial:
    a. chemotherapy ≥ 28 days
    b. antibody treatment ≥ 14 days
    c. kinase inhibitors (see also exclusion criterion 6), BCL2-antagonists or immuno-modulatory agents ≥ 3 days
    d. corticosteroids may be applied until the start of the study therapy, these have to be reduced to an equivalent of ≤ 20mg prednisolone per day during treatment
    11. Signed informed consent and, in the investigator’s judgment, able to comply with the study protocol.
    E.4Principal exclusion criteria
    1. >1 prior CLL-specific therapy (corticosteroid treatment is not counted as prior treatment; within the last 10 days before start of study treatment, only corticosteroid dose equivalents up to 20 mg prednisolone are permitted).
    2. Transformation of CLL to aggressive NHL (Richter’s transformation or pro-lymphocytic leukaemia).
    3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML).
    4. Patients with uncontrolled autoimmune haemolytic anaemia or immune thrombocyto-penia.
    5. Prior exposure to acalabrutinib.
    6. Progression during previous treatment with another BTK inhibitor, and/or presence of known mutations associated with resistance to therapy, e.g. Bruton´s Tyrosine Kinase and Phospholipase C Gamma 2 (PLCg2)
    a. Please note: Patients with a progression during previous treatment with an-other BTK inhibitor, as well as patients with a known resistance mutation (e.g. BTK-/PLCg2) are excluded from study participation. However, patients who progressed after termination of treatment with other BTK inhibitors or who stopped treatment due to intolerance are eligible for participation.
    7. Uncontrolled concomitant malignancy, i.e. any concomitant malignancy that may compromise the assessment of CLL stage and the response assessment of the study treatment.
    8. Eastern Cooperative Oncology Group Performance Status (ECOG) >3.
    9. Uncontrolled or active infection (including positive SARS-Cov-2 PCR result)
    10. Patients with known infection with human immunodeficiency virus (HIV).
    11. Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 3 months of screening, or any class 4 cardiac disease as defined by the New York Heart Association Functional Classifica-tion at screening.
    i. Please note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
    12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
    13. Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathesis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure ≤ 4 weeks or stroke/intracranial hemorrhage ≤ 6 months.
    14. Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
    15. Requirement of therapy with strong CYP3A4 inhibitors/inducers or anticoagulant with phenprocoumon (marcumar) or other vitamin K-antagonists
    i. Please note: Switch to alternative anticoagulants for vitamin K antago-nists is permitted.
    16. Inability to swallow tablets.
    17. Legal incapacity.
    18. Prisoners or subjects who are institutionalized by regulatory or court order.
    19. Persons who are in dependence to the sponsor or an investigator.
    E.5 End points
    E.5.1Primary end point(s)
    Overall response rate (ORR) at initial response assessment (cycle 7, day 1 = approx. 6 months after initiation of therapy).
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint can be analysed as soon as all enrolled patients who did not discontinue prematurely have achieved the initial response assessment at cycle 7 day 1 (= approx. 6 months after initiation of therapy). This will trigger the time point of the analysis of the primary and secondary endpoints.
    E.5.2Secondary end point(s)
    - ORR at final restaging (cycle 25, day 1 = approx. 24 months af-ter initiation of therapy).
    - Overall survival (OS).
    - Progression free survival (PFS).
    - Event-free survival (EFS).
    - Duration of response.
    - Time to next CLL treatment (TTNT).
    - Feasibility parameters:
    o Modification of treatment and reasons.
    o Treatment discontinuation: early discontinuation of treat-ment and reasons.
    o Treatment exposure: total cumulative dose, dose intensi-ty, time on treatment (any dose), time on treatment (full dose), days with 0 dose.
    - Safety parameters: Type, frequency, and severity of
    o adverse events (AEs) and
    o adverse events of special interest (AESI) including falls and delirium as typical adverse geriatric outcomes and their relationship to study treatment.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The primary endpoint can be analysed as soon as all enrolled patients who did not discontinue prematurely have achieved the initial response assessment at cycle 7 day 1 (= approx. 6 months after initiation of therapy). This will trigger the time point of the analysis of the primary and secondary endpoints.
    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) 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 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 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    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 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
    The end of the clinical trial is defined as the theoretical timepoint where the last patient included into the trial (LPI) reaches the final restaging (cycle 25 day 1), independently from whether the patient reaches it or not.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 years4
    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: 1
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 52
    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 state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 37
    F.4.2.2In the whole clinical trial 53
    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)
    As acalabrutinib recently received approval for market authorization in Europe in 2020, treatment can be continued via routine prescription after the end of the clinical trial. If not commercially available at the end of the trial acalabrutinib will be further provided by the pharmaceutical sponsor of this trial, AstraZeneca.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-09-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-24
    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-Thu Apr 25 07:37:17 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA