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   43841   clinical trials with a EudraCT protocol, of which   7281   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:2011-005491-41
    Sponsor's Protocol Code Number:B1931022
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-09-25
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2011-005491-41
    A.3Full title of the trial
    An Open-label, Randomized Phase 3 Study of Inotuzumab Ozogamicin Compared to a
    Defined Investigator’s Choice in Adult Patients with Relapsed or Refractory
    CD22-Positive Acute Lymphoblastic Leukemia (ALL)
    Studio clinico di fase 3, randomizzato, in aperto per confrontare l'inotuzumab ozogamicina ad una terapia scelta dallo sperimentatore fra regimi predefiniti in pazienti adulti con leucemia linfoblastica acuta (LLA) positiva per CD22, recidivante o refrattaria.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 3 Study of Inotuzumab Ozogamicin versus Investigator’s Choice of Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia
    Studio di fase 3 di inotuzumab ozogamicina rispetto alla chemioterapia di scelta dallo sperimetatore per pazienti con leucemia linfoblastica recidiva o refrattaria acuta
    A.4.1Sponsor's protocol code numberB1931022
    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 SponsorPFIZER INC.
    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 supportPfizer Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc.
    B.5.2Functional name of contact pointClinical Trials.gov Call Center
    B.5.3 Address:
    B.5.3.1Street Address235 E 42nd Street
    B.5.3.2Town/ cityNey York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+001 800 7181021
    B.5.5Fax number+001 303 7391119
    B.5.6E-mailClinicalTrials.govCallCenter@pfizer.com
    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.3.1Product nameInotuzumab Ozogamicin
    D.3.2Product code PF-05208773
    D.3.4Pharmaceutical form Powder 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.3.9.2Current sponsor codeCMC-544
    D.3.9.3Other descriptive nameinotuzumab ozogamicin
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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) 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 Yes
    D.3.11.13.1Other medicinal product typecalicheamicin-conjugated humanized anti-CD22 monoclonal IgG4 antibody
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Cytosar, 500 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 Powder 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 INNCYTARABINE
    D.3.9.1CAS number 147-94-4
    D.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number.5
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Cytosar, 500 mg
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 Powder 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 INNCYTARABINE
    D.3.9.1CAS number 147-94-4
    D.3.9.4EV Substance CodeSUB06880MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    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 Neupogen 600 ug/ml
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe BV
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection
    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 INNFILGRASTIM
    D.3.9.1CAS number 121181-53-1
    D.3.9.4EV Substance CodeSUB07627MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number600
    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 Yes
    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.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    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 Neupogen 960 ug/ml
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe BV
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection
    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 INNFILGRASTIM
    D.3.9.1CAS number 121181-53-1
    D.3.9.4EV Substance CodeSUB07627MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number960
    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 Yes
    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.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    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 Fludarabine Actavis 50mg
    D.2.1.1.2Name of the Marketing Authorisation holderActavis UK Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 injection
    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 INNFLUDARABINE
    D.3.9.1CAS number 21679-14-1
    D.3.9.4EV Substance CodeSUB07678MIG
    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 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.IMP: 7
    D.1.2 and D.1.3IMP RoleComparator
    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 Mitoxantrone (Mitozantrone) 2mg/ml
    D.2.1.1.2Name of the Marketing Authorisation holderHospira Uk Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 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 INNMITOXANTRONE
    D.3.9.1CAS number 65271-80-9
    D.3.9.4EV Substance CodeSUB09012MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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
    Relapsed or Refactory B Cell Acute Lymphoblastic leukemia
    Leucemia linfoblastica acuta (LLA) da precursori delle cellule B, recidivante o refrattaria
    E.1.1.1Medical condition in easily understood language
    Relapsed or Refactory Acute Lymphoblastic leukemia
    Leucemia linfoblastica acuta recidivante o refrattaria
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10066104
    E.1.2Term Precursor B-lymphoblastic leukaemia acute
    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
    To compare the hematological remission, defined as CR (both CR and CRi), as reported by the external independent endpoint adjudication committee, in patients with relapsed/refractory ALL randomized to receive inotuzumab ozogamicin (Arm A) versus patients randomized to receive active comparator (Arm B).
    Confrontare la remissione ematologica, definita come RC (sia RC sia RCi), come riportato da una commissione giudicatrice indipendente esterna, in pazienti con LLA recidivante o refrattaria randomizzati a ricevere l’inotuzumab ozogamicina (Braccio A) verso pazienti randomizzati a ricevere un comparatore attivo (Braccio B).
    E.2.2Secondary objectives of the trial
    Safety and efficacy endpoints will be compared between the inotuzumab ozogamicin arm and the active comparator arm and will include: Key Secondary Objective: • To compare the overall survival (OS) of patients with relapsed/refractory ALL. Other Secondary Objectives: • To compare the duration of response (DoR); • To compare the progression-free survival (PFS); • To compare the time to progression (TTP); • To compare the rate of stem-cell transplantation in patients; • To characterize the safety and tolerability including the rate of VOD (veno-occlusive disease)/SOS (sinusoidal obstruction syndrome) following allogeneic stem cell transplant; • To assess minimal residual disease (MRD) levels and cytogenetics in patients achieving a CR/CRi;
    Confrontare gli endpoint di sicurezza ed efficacia tra il braccio dell’inotuzumab ozogamicina e quello del comparatore attivo includendo: Obiettivo chiave secondario • Confronto della sopravvivenza globale (SG) dei pazienti con LLA recidivante o refrattaria. Altri obiettivi secondari • Confronto della durata della risposta (DdR); • Confronto della sopravvivenza libera da progressione (SLP); • Confronto del tempo di progressione (TdP) • Confronto del tasso di trapianto di cellule staminali nei pazienti; • Caratterizzazione di sicurezza e tollerabilità, incluso il tasso di MVO (malattia veno-occlusiva)/SOS (sindrome di ostruzione sinusoidale), a seguito di trapianto allogenico di cellule staminali; • Analisi dei livelli di malattia minima residua (MMR) e analisi citogenetica in pazienti che raggiungono una RC/RCi;
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Relapsed or refractory CD22-positive ALL (ie, ≥20% blasts CD22-positive) due to receive either salvage 1 or salvage 2 therapy and for which either arm of randomized study therapy offers a reasonable treatment option. Ph+ ALL patients must have failed treatment with at least 1 second generation tyrosine kinase inhibitor; 2. Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy; 3. Bone marrow involvement with ≥5% lymphoblasts; 4. Age 18 years or older; 5. ECOG performance status 0-2; 6. Adequate liver function, including total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN. If organ function abnormalities are considered due to tumor, total serum bilirubin must be ≤2 x ULN; 7. Serum creatinine ≤1.5 x upper limit of normal (ULN) or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥40 mL/min; 8. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for a minimum of 90 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria): • Have undergone hysterectomy or bilateral oophorectomy; or • Have medically confirmed ovarian failure; or • Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause. 9. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study; 10. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
    1. Pazienti con LLA CD22-positiva recidivante o refrattaria (ovvero ≥20% blasti CD22-positivi) che dovranno ricevere la prima terapia di salvataggio o la seconda e per cui uno dei due bracci della terapia di studio randomizzata offra una opzione terapeutica ragionevole. I pazienti LLA Ph+ dovranno aver fallito il trattamento con almeno 1 inibitore della tirosina chinasi di seconda generazione; 2. I pazienti in prima terapia di salvataggio con recidiva tardiva devono essere considerati dei candidati inadeguati per la reinduzione con la terapia iniziale; 3. Coinvolgimento del midollo osseo con ≥ 5% di linfoblasti; 4. Età minima di 18 anni; 5. Stato di performance dell’ECOG 0-2; 6. Funzionalità epatica adeguata, compresa la bilirubina totale del siero ≤ 1,5 x ULN a meno che il paziente non presenti una sindrome di Gilbert documentata e aspartato transaminasi (AST) e alanina transaminasi (ALT) ≤ 2,5 x ULN. Se le anormalità delle funzioni dell’organo sono ritenute causate dal tumore, la bilirubina totale del siero deve essere ≤ 2 x ULN. 7. Creatinina sierica &lt;1,5 x limite superiore del valore normale (ULN) o qualsiasi livello di creatinina sierica associata con una clearance della creatinina misurata o calcolata come ≥ 240 ml/min; 8. I pazienti di sesso maschile e femminile in età fertile devono acconsentire ad utilizzare un metodo altamente efficace di contraccezione durante lo studio e per un minimo di 90 giorni dopo la somministrazione dell’ultima dose di trattamento assegnato. Un/a paziente è in età fertile se, secondo il giudizio dello sperimentatore, è biologicamente in grado di avere figli ed è sessualmente attivo/a. Le pazienti che non sono in età fertile (cioè, soddisfano almeno uno dei seguenti criteri): • sono state sottoposte a isterectomia o ovariectomia bilaterale, oppure • presentano una insufficienza ovarica confermata a livello medico, oppure • hanno ricevuto una conferma medica di essere in post-menopausa (cessazione delle mestruazioni regolari per almeno 12 mesi consecutivi senza altra causa patologica o fisiologica). 9. Presentano evidenza di un documento di consenso informato firmato e datato personalmente attestante che il/la paziente (o un suo rappresentante legale) è stato/a informato/a di tutti gli aspetti relativi allo studio; 10. Sono pazienti disposti e in grado di rispettare le visite programmate, il programma di trattamento, gli esami di laboratorio e le altre procedure di studio.
    E.4Principal exclusion criteria
    1. Isolated extramedullary relapse (ie, testicular or CNS); 2. Burkitt’s or mixed lineage leukemia; 3. Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion; 4. Prior chemotherapy within ≤2 weeks before randomization with the following exceptions: steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine, thioguanine, and tyrosine kinase inhibitors are permitted within 2 weeks of randomization as maintenance or to reduce the peripheral blood blast count. Patients must have recovered from acute non hematologic toxicity (to ≤ Grade 1) of all previous therapy prior to enrollment; 5. Prior monoclonal antibodies within 6 weeks of randomization; 6. Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy ≤4 months before randomization. Patients must have completed immunosuppression therapy for treatment of GvHD prior to enrollment. At randomization, patients must not have ≥ Grade 2 acute GvHD, or extensive chronic GvHD; 7. Peripheral absolute lymphoblast count ≥10,000 /μL (treatment with hydroxyurea and/or steroids is permitted within 2 weeks of randomization to reduce the WBC count); 8. Known systemic vasculitides (eg, Wegener’s granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease); 9. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice; 10. Major surgery within ≤4 weeks before randomization; 11. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition); 12. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for ≥2 years; 13. Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 45%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure; 14. Patients with active heart disease (NYHA class ≥3 as assessed by history and physical examination); 15. QTcF >470 msec (based on the average of 3 consecutive ECGs); 16. Myocardial infarction ≤6 months before randomization; 17. History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of AV block unless a permanent pacemaker has been implanted;
    1. Recidiva extramidollare isolata (es.: testicolare o del sistema nervoso centrale); 2. Leucemia di Burkitt o con lineage ambiguo; 3. Leucemia con sistema nervoso centrale (CNS) attivo, come definito dall’inequivocabile evidenza morfologica dei linfoblasti nel liquido cerebrospinale (CSF), uso di un trattamento locale mirato del CNS per la malattia attiva entro i precedenti 28 giorni, leucemia con coinvolgimento sintomatico del CNS (paralisi dei nervi cranici o altre disfunzioni neurologiche significative) entro 28 giorni. La profilassi con farmaci per via intratecale non è un motivo di esclusione; 4. Una precedente chemioterapia entro ≤ 2 settimane prima della randomizzazione con le seguenti eccezioni: steroidi, idrossiurea, mercaptopurine orali, metotrexato, vincristina, tioguanina e inibitori della tirosina chinasi sono permessi entro 2 settimane dalla randomizzazione come mantenimento o per ridurre il numero di blasti nel sangue periferico. I pazienti devono essere guariti da tossicità acute non ematologiche (di grado ≤1) derivanti da tutte le terapie precedenti prima dell’arruolamento. 5. Precedente assunzione di anticorpi monoclonali entro 6 settimane dalla randomizzazione; 6. Precedente trapianto di cellule staminali ematopoietiche allogeniche (HSCT) o altre tipi di immunoterapia anti-CD22 effettuati ≤ 4 mesi prima della randomizzazione. I pazienti dovranno aver completato la terapia con gli immunosoppressori per il trattamento della GvHD prima dell’arruolamento. Al momento della randomizzazione, i pazienti non dovranno presentare GvHD &gt; di grado 2 in fase acuta, e neanche GvHD estesa cronica; 7. Numero assoluto di linfoblasti periferici ≥ 10.000 /μL (trattamenti con idrossiurea e/o steroidi sono consentiti entro 2 settimane dalla randomizzazione per ridurre la conta dei globuli bianchi); 8. Vasculiti sistemiche note (es. granulomatosi di Wegener, poliarterite nodosa, Lupus eritematoso sistemico), immunodeficienza primaria o secondaria (come infezione da HIV o malattie infiammatorie gravi); 9. Infezione da epatite B o C in corso o cronica come evidenziato rispettivamente dall’antigene di superficie dell'epatite B e dalla positività degli anticorpi anti-epatite C o dalla sieropositività nota per il virus dell’immunodeficienza umana (HIV). Potrebbe essere necessario eseguire il test per l’HIV in conformità alla normativa vigente o alla pratica locale; 10. Intervento di chirurgia maggiore entro ≤ 4 settimane prima della randomizzazione; 11. Condizione medica controllata instabile o grave (es., funzione cardiaca instabile o condizione polmonare instabile); 12. Neoplasia attiva concomitante diversa da un tumore della pelle non-melanoma, carcinoma in situ della cervice o tumore alla prostata localizzato trattato in maniera definitiva con radiazioni o interventi chirurgici. I pazienti con tumori maligni precedenti sono idonei a condizione che siano stati liberi da malattia per ≥ 2 anni; 13. Funzione cardiaca, misurata tramite la frazione di eiezione ventricolare sinistra (LVEF) che è inferiore al 45% o la presenza di insufficienza cardiaca congestizia di stadio III o IV della New York Heart Association (NYHA); 14. Pazienti con malattia cardiaca attiva (classe NYHA ≥ 3 sulla base della valutazione dell’anamnesi e dell’esame obiettivo); 15. QTcF &gt; 470 msec (sulla base della media di 3 ECG consecutive); 16. Infarto del miocardio &lt; 6 mesi prima della randomizzazione; 17. Storia di aritmia ventricolare clinicamente significativa o sincope inspiegata ritenuta di natura non vasovagale o stati di bradicardia cronica come blocco seno-atriale o un grado superiore di blocco atrio-ventricolare (AV) a meno che sia stato impiantato un pacemaker permanente;
    E.5 End points
    E.5.1Primary end point(s)
    CR and CRi.
    • RC e RCi.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Dependent on individual patient response
    A seconda della risposta individuale del paziente
    E.5.2Secondary end point(s)
    • OS (Key secondary endpoint); • DoR; • PFS; • TTP; • Number of Transplants; • Adverse events and laboratory abnormalities (CTCAE v3.0 grade, timing, seriousness and relatedness); • MRD and cytogenetics in responding patients; • PK; • EORTC QLQ-C30 and EQ-5D.
    • SG (obiettivo chiave secondario); • DdR; • SLP; • Numero di trapianti; • Eventi avversi e anormalità di laboratorio (grado, tempistica, serietà e interdipendenza secondo i CTCAE nella versione 3.0); • MRD e citogenetica in pazienti con risposta; • PK; • Questionari EORTC QLQ-C30 e EQ-5D.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Dependent on individual patient response
    A seconda della risposta individuale del paziente
    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 Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    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.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 EEA40
    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
    Argentina
    Brazil
    Canada
    China
    Croatia
    Japan
    Korea, Democratic People's Republic of
    Korea, Republic of
    Singapore
    Taiwan
    Thailand
    Ukraine
    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
    End of trial in all participating countries is defined as the Last Patient Last Visit (inclusive of long term follow-up visits, see section 6.4 of the protocol) unless stopped earlier by the external data monitory committee.
    La conclusione dello studio in tutti i Paesi partecipanti è definita come l'ultima visita dell'ultimo soggetto (incluso le visite di follow-up a lunfo termine ved sez. 6.4 del protocollo) a meno che non viene terminato prima su richiesta del E-DMC
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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 No
    F.1.1Number of subjects for this age range: 0
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 300
    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)
    normal treatment for all
    trattamento normale per tutti
    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 Decision2012-11-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-09-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-01-04
    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA