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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43715   clinical trials with a EudraCT protocol, of which   7255   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 ).  
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    EudraCT Number:2015-005317-68
    Sponsor's Protocol Code Number:ACE-CL-208
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-05-19
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2015-005317-68
    A.3Full title of the trial
    A Phase 2 Study of the Efficacy and Safety of ACP-196 in Subjects with Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
    Estudio de fase II de eficacia y seguridad de ACP-196 en sujetos con leucemia linfocítica crónica (LLC) resistentes o recidivantes e intolerantes al tratamiento con ibrutinib
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2 Study of the Efficacy and Safety of ACP-196 in Subjects with Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy
    Estudio de fase II de eficacia y seguridad de ACP-196 en sujetos con leucemia linfocítica crónica (LLC) resistentes o recidivantes e intolerantes al tratamiento con ibrutinib
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberACE-CL-208
    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 SponsorAcerta Pharma, BV
    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 supportAcerta Pharma
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAcerta
    B.5.2Functional name of contact pointPriti Patel,Senior Medical Director
    B.5.3 Address:
    B.5.3.1Street Address2200 Bridge Parkway, Suite 202
    B.5.3.2Town/ cityRedwood City
    B.5.3.3Post codeCA 64065
    B.5.3.4CountryUnited States
    B.5.4Telephone number001650787 4817
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code ACP-196
    D.3.4Pharmaceutical form Capsule
    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.3.9.2Current sponsor codeACP-196
    D.3.9.3Other descriptive nameACP-196
    D.3.9.4EV Substance CodeSUB166233
    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. 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) 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
    High Risk Chronic Lymphocytic Leukemia
    Leucemia linfocítica crónica de alto riesgo
    E.1.1.1Medical condition in easily understood language
    High Risk Chronic Lymphocytic Leukemia
    Leucemia linfocítica crónica de alto riesgo
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10008976
    E.1.2Term Chronic lymphocytic leukemia
    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 check the efficacy of acalabrutinib in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy
    Evaluar la eficacia de acalabrutinib en sujetos con LLC recidivante/resistente que no toleran el tratamiento con ibrutinib.
    E.2.2Secondary objectives of the trial
    To evaluate the safety and tolerability of acalabrutinib in subjects with relapsed/refractory CLL who are intolerant of ibrutinib therapy
    - To determine the effect of acalabrutinib on peripheral blood B cells, T cells, NK cells, and MDSCs.
    - To evaluate potential predictive biomarkers and mechanisms of resistance for the disease.
    Evaluar la seguridad y la tolerabilidad de acalabrutinib en sujetos con LLC recidivante/resistente que no toleran el tratamiento con ibrutinib.
    - Determinar el efecto de acalabrutinib en linfocitos B, linfocitos T, linfocitos citolíticos naturales y CSOM en sangre periférica.
    - Evaluar posibles biomarcadores predictivos y mecanismos de resistencia para la enfermedad.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1-Prior diagnosis of CLL that meets published diagnostic criteria (Hallek 2008)
    2-Must have received ? 1 prior therapy for CLL and not be appropriate for treatment or retreatment with purine analogue-based therapy
    3-Intolerant of ibrutinib, defined as the subject has discontinued ibrutinib therapy due to Grade 3 or 4 AEs that persisted in spite of optimal supportive care measures OR patients who had Grade 2 AEs related to ibrutinib therapy, in spite of optimal supportive care measures, that persisted for ? 2 weeks or that recurred ? 2 times whether dose was reduced or discontinued.
    4-ECOG performance status of ? 2
    1-Diagnóstico previo de LLC que cumple los criterios de diagnóstico publicados (Hallek 2008)
    2-Debe haber recibido ? 1 tratamiento previo para la LLC y no ser adecuado para el tratamiento o la repetición del tratamiento con análogos de la purina
    3-Intolerancia al ibrutinib, lo que se define como que el sujeto ha discontinuado el tratamiento con ibrutinib debido a AA de grado 3 o 4 que persistieron a pesar del tratamiento sintomático óptimo, O BIEN pacientes que presentaron AA de grado 2 relacionados con ibrutinib, a pesar del tratamiento sintomático óptimo, que persistieron durante ? 2 semanas o que reaparecieron ? 2 veces, aunque se redujera o discontinuara la dosis.
    4-Estado funcional ECOG ? 2.
    E.4Principal exclusion criteria
    1-Ongoing Grade 3 or 4 AE attributed to ibrutinib therapy. Note: Patients may be eligible for enrollment once the ibrutinib-related AE improves to Grade ? 2.
    2-Treatment with systemic anticancer therapy for CLL is prohibited between discontinuation of ibrutinib and enrollment on this trial.
    3-Prior exposure to a BCL-2 inhibitor (eg, ABT-199).
    4-Prior malignancy (other than CLL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the subject has been disease free for ? 2 years.
    1-AA de grado 3 o 4 en curso atribuidos al tratamiento con ibrutinib. Nota: Los pacientes pueden ser elegibles para la inclusión una vez que el AA relacionado con ibrutinib mejore hasta un grado ? 2.
    2-Está prohibido el tratamiento con antineoplásicos sistémicos para la LLC entre el momento de la discontinuación de la administración de ibrutinib y la inclusión en este ensayo.
    3-Exposición previa a un inhibidor de BCL-2 (como ABT-199).
    4-Neoplasia maligna previa (distinta de la LLC), a excepción de carcinoma basocelular o carcinoma espinocelular, cáncer localizado u otro tipo de cáncer adecuadamente tratado del que el sujeto haya estado libre durante ? 2 años .
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy will be evaluated based on the IWCLL 2008 criteria.
    The primary efficacy endpoint is Overall Response Rate (ORR) assessed by the investigators at the end of treatment.
    La eficacia se evaluará sobre la base de los criterios del IWCLL 2008. El criterio principal de valoración de la eficacia es la Tasa de Respuesta Global (TRG) evaluada por los investigadores al finalizar el tratamiento.
    E.5.1.1Timepoint(s) of evaluation of this end point
    See section above.
    Ver sección anterior.
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints are:
    - Duration of Response (DOR)
    - Progression-Free Survival (PFS)
    - Time to Next Treatment (TTNT)
    - Overall Survival (OS)

    The safety of acalabrutinib will be characterized by laboratory assessments performed throughout the study and the type, frequency, severity, and attribution of AEs, or AEs leading to discontinuation of study treatment.

    The exploratory objectives will be evaluated through pharmacodynamic and biomarker parameters. The occupancy of Btk by acalabrutinib will be measured in PBMCs with the aid of a biotin-tagged acalabrutinib analogue probe. The effect of acalabrutinib on B cells, NK cells (CD56+), T cells (CD3+, CD4+, CD8+ levels), and MDSCs (HLA-DR- CD14+CD11b+ CD33+ levels) will also be evaluated. Genotyping for Btk, p53, and PLC? mutations will be performed.
    Los criterios secundarios de valoración de la eficacia son:
    - Duración de la respuesta (DDR)
    - Supervivencia sin progresión (SSP)
    - Tiempo hasta el siguiente tratamiento (THST)
    - Supervivencia Global (SG)

    La seguridad de acalabrutinib se describirá por medio de análisis de laboratorio realizados a lo largo del estudio y el tipo, la frecuencia, la intensidad y la atribución de los AA, o los AA que conducen a la discontinuación del tratamiento del estudio.

    Los objetivos exploratorios se evaluarán mediante parámetros farmacodinámicos y de biomarcadores. La ocupación de Btk por parte de acalabrutinib se medirá en CMSP con ayuda de una sonda de análogo de acalabrutinib marcado con biotina. También se evaluará el efecto de acalabrutinib sobre los linfocitos B, los linfocitos citolíticos naturales (NK) (CD56+), linfocitos T (concentraciones de CD3+, CD4+, CD8+), y CSOM (concentraciones de HLA-DR-, CD14+, CD11b+, CD33+). Se llevará a cabo la genotipificación de las mutaciones de Btk, p53 y PLC?.
    E.5.2.1Timepoint(s) of evaluation of this end point
    See section above.
    Ver sección anterior.
    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 Yes
    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. 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    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
    United Kingdom
    United States
    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 end of trial is defined as the point when the last subject enrolled completes end of Cycle 36 or withdraws for any reason and completes the 30-day SFU visit (if applicable), whichever occurs first.
    El final del ensayo se define como el punto en el que el último sujeto incluido completa el ciclo 36 o se retira por cualquier razón y finaliza la visita de SS de los 30 días (si procede), lo que ocurra antes.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months8
    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 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: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 80
    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)
    After completing study regimen treatment can continue until the end of the trial for subjects without disease progression and who are tolerating therapy after discussion with the medical monitor.
    El tratamiento puede continuar hasta el final del ensayo para los sujetos sin progresión de la enfermedad y que toleran el tratamiento, tras consultarlo con el monitor médico.
    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 Decision2016-03-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-02-25
    P. End of Trial
    P.End of Trial StatusCompleted
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    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
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