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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   41449   clinical trials with a EudraCT protocol, of which   6808   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    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

    Download PDF

    Clinical Trial Results:
    90-Yttrium-labelled anti-CD66 monoclonal antibody as part of a reduced intensity conditioning regimen prior to allogeneic haematopoietic stem cell transplantation: an open label, dose escalating phase I study in children with relapsed/refractory leukaemia

    Summary
    EudraCT number
    2013-000015-24
    Trial protocol
    GB  
    Global end of trial date
    14 May 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    17 Apr 2021
    First version publication date
    17 Apr 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    07MI05
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04082286
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Great Ormond Street Hospital for Children NHS Foundation Trust
    Sponsor organisation address
    30 Guilford Street, London, United Kingdom,
    Public contact
    Dr. Robert Chiesa, Dr. Robert Chiesa, 44 2079052863, CTIMP.Safety@gosh.nhs.uk
    Scientific contact
    Dr. Robert Chiesa, Great Ormond Street Hospital for Children NHS Foundation Trust, robert.chiesa@gosh.nhs.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Mar 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 May 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To determine whether a radiolabelled antibody that tergets the bone marrow (the anti-CD66) can be administered safely to children as part of the preparative treatment prior to haematopoietic stem cell transplantation. To evaluate the safety (and maximum tolerated dose) and feasibility of targeted radiotherapy delivered by 90-Yttrium-labelled anti-CD66 monoclonal antibody within a reduced intensity conditioning regimen in children with relapsed/refractory leukaemia undergoing allogeneic haematopoietic stem cell transplantation.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines, the general principles indicated in the Declaration of Helsinki, and all applicable regulatory requirements. Prior to initiation at each study center, the study protocol was reviewed by an Independent Ethics Committee (IEC). All subjects were to provide written informed consent prior to entering the study and before initiation of any study-related procedure (including administration of investigational product). The investigator was responsible for explaining the benefits and risks of participation in the study to each subject or the subject’s legally acceptable representative and for obtaining written informed consent.
    Background therapy
    Patients would receive a reduced intensity conditioning regimen consisting on Fludarabine (150 mg/sqm), Treosulfan (30-42 g/sqm), Thiotepa (10 mg/kg) +/- Alemtuzumab or ATG will be administered after the infusion of 90Y-labelled anti-CD66 monoclonal antibody, starting from day – 8 prior to transplant.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    26 May 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 9
    Worldwide total number of subjects
    9
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    5
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study was conducted at 2 sites in the UK (GOSH and UCLH) between 26-May-2016 (First Patient enrolment) and 15-Aug-2019 (Last Patient enrolment).

    Pre-assignment
    Screening details
    14 subjects were screened and consented for this study, but 5 patients failed the screeneing phase. Nine patients were eventually recruited and treated with radio-immunotherapy

    Period 1
    Period 1 title
    Baseline & Overall Study Period (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded
    Blinding implementation details
    not applicable

    Arms
    Arm title
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Arm description
    Patients enrolled into this study received a single dose of Yttrium-90 labelled anti-CD66 antibody as part of a reduced toxicity conditioning regimen, prior to allogeneic haematopoietic stem cell transplant
    Arm type
    Experimental

    Investigational medicinal product name
    Indium-111-labelled anti CD66 monoclonal antibody
    Investigational medicinal product code
    In111i
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 MBq/sqm, given as a single dose iv over 15-30 minutes

    Investigational medicinal product name
    Yttrium-90 labelled anti CD66 monoclonal antibody
    Investigational medicinal product code
    Y90
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    0.5-3 mg of antibody protein (with increasing doses of Yttrium90, according to protocol) infused iv as a single dose

    Number of subjects in period 1
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Started
    9
    Completed
    9

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Baseline & Overall Study Period
    Reporting group description
    Children with relapsed/refractory leukaemia

    Reporting group values
    Baseline & Overall Study Period Total
    Number of subjects
    9 9
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    5 5
        Adolescents (12-17 years)
    4 4
        Adults (18-64 years)
    0 0
        From 65-84 years
    0 0
        85 years and over
    0 0
    Gender categorical
    We treated 5 femaled and 4 males
    Units: Subjects
        Female
    5 5
        Male
    4 4

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Reporting group description
    Patients enrolled into this study received a single dose of Yttrium-90 labelled anti-CD66 antibody as part of a reduced toxicity conditioning regimen, prior to allogeneic haematopoietic stem cell transplant

    Primary: Safety endpoint: assessment of dose limiting toxicity

    Close Top of page
    End point title
    Safety endpoint: assessment of dose limiting toxicity [1]
    End point description
    Dose-limiting toxicity (DLT) was defined as follows, using the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 4.0) : a) graft failure: neutrophils < 0.5 x 109/L by day + 45 post transplant (unless clearly due to concomitant infections, other medications or poor stem cell dose/viability); b) Hepatic/gastrointestinal toxicity (excluding oral mucositis) by day +30 post transplant: ≥ grade 3, excluding causes such as concomitant drugs, infections or GvHD; c) Gastrointestinal toxicity (oral mucositis) by day +30 post transplant: > grade 3, excluding causes such as concomitant drugs, infections or GvHD; d) Neurological toxicity by day +30 post transplant: ≥ grade 3, excluding causes such asconcomitant drugs or infections; e) Pulmonary toxicity by day +30 post transplant: ≥ grade 3, excluding infectious causes, peri-engraftment syndrome or concomitant drugs; f) Cutaneous toxicity by day +30 post transplant: ≥ grade 3, excluding concomitant drug reactions, infe
    End point type
    Primary
    End point timeframe
    Assessment of dose limiting toxicity (DLT) within 30 days post-stem cell transplant
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Children received increasing doses of targeted radio-immunotherapy, with a max infused activity of 47 MBq/kg and a max absorbed dose to the bone marrow= 45 Gy. As the antibody used in this trial expired, the study ended prematurely and we couldn't escalate the dose up to 55 MBq/kg. Nevertheless children in the last cohort received a high dose of radiation to the bone marrow and RIT was extremely well tolerated by 9/9 children. None experienced a Dose Limiting Toxicity.
    End point values
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Number of subjects analysed
    9
    Units: 0-10
        Number of patients experiencing DLT
    0
    No statistical analyses for this end point

    Secondary: Disease response after 90Yttrium-labelled anti-CD66 monoclonal antibody

    Close Top of page
    End point title
    Disease response after 90Yttrium-labelled anti-CD66 monoclonal antibody
    End point description
    To assess disease response after RIT and stem cell transplant.
    End point type
    Secondary
    End point timeframe
    Disease response at 1 year post-stem cell transplant
    End point values
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Number of subjects analysed
    9
    Units: 0-9
        Patients in complete remisison 1 year after RIT
    2
    No statistical analyses for this end point

    Secondary: Timing of myeloid and platelet recovery after allogeneic haematopoietic stem cell transplantation

    Close Top of page
    End point title
    Timing of myeloid and platelet recovery after allogeneic haematopoietic stem cell transplantation
    End point description
    Timing of myeloid and platelet recovery after allogeneic haematopoietic stem cell transplantation
    End point type
    Secondary
    End point timeframe
    Timing of myeloid and platelet recovery within 2 months post-stem cell transplantation
    End point values
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Number of subjects analysed
    9
    Units: median
    median (full range (min-max))
        Median time to neutrophil recovery
    17 (11 to 31)
        Median time to platelet recovery
    28 (14 to 43)
    No statistical analyses for this end point

    Secondary: Donor engraftment rate and quality of chimerism after allogeneic haematopoietic stem cell transplant

    Close Top of page
    End point title
    Donor engraftment rate and quality of chimerism after allogeneic haematopoietic stem cell transplant
    End point description
    Analysis of donor engrfatment after BMT.
    End point type
    Secondary
    End point timeframe
    Chimerism d+30 post transplant
    End point values
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Number of subjects analysed
    9
    Units: percent
    number (not applicable)
        Percentage of children with full donor engraftment
    100
    No statistical analyses for this end point

    Secondary: Biodistribution of Indium-111, after imaging with gamma camera / SPECT-CT scans and blood samples

    Close Top of page
    End point title
    Biodistribution of Indium-111, after imaging with gamma camera / SPECT-CT scans and blood samples
    End point description
    Biodistribution of In111-labelled anti-CD66 ab after infusion (dosimetry)
    End point type
    Secondary
    End point timeframe
    Biodistribution of In111-labelled anti-CD66 ab within 7 days post infusion
    End point values
    Infusion of Yttrium-90 labelled monoclonal anti-CD66 antibody
    Number of subjects analysed
    9
    Units: percent
    number (not applicable)
        % children with good In-111 biodistribution
    100
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Adverse events were recorded from Study enrolment to 1 year post-stem cell transplant
    Adverse event reporting additional description
    Adverse events were described and graded using the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 4.0).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    NCI
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Adverse events RIT phase 1 study
    Reporting group description
    Children with relapsed/refractory leukaemia undergoing allogeneic haematopoietic stem cell transplant after receiving a infusion of Yttrium-90 labelled anti-CD66 monoclonal antibody, as part of a reduced toxicity conditioning regimen.

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: As the Radio Immuno Therapy (RIT) was followed by chemotherapy and an allogeneic haematopoietic stem cell transplant, all children experienced multiple non-serious AEs, as expected. It would be difficult to include them all in this report owing to huge number and as most of these AEs were related to the transplant, rather than the radio-immunotherapy.
    Serious adverse events
    Adverse events RIT phase 1 study
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 9 (100.00%)
         number of deaths (all causes)
    5
         number of deaths resulting from adverse events
    1
    Blood and lymphatic system disorders
    Leukaemia
    Additional description: Relapse of leukaemia, switched to palliative care.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Oxygen saturation decreased
    Additional description: Respiratory failure post leukaemia relapse, unrelated to IMP. Switched to palliative care.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nervous system disorders
    Seizure
    Additional description: Seizures resolved with medications.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Dehydration
    Additional description: Vomiting, weakness, decreased renal function. Resolved
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Increased ALT
    Additional description: Self-resolved NCI grade III increased ALT, not related to IMP.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Venoocclusive disease
    Additional description: VOD post BMT, unrelated to IMP, but due to other risk factors (second BMT, conditioning regimen, azole toxicity). Resolved.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Febrile neutropenia
    Additional description: Febrile neutropenia, resolved with antibiotics
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Sphingomonas paucimobilis infection
    Additional description: Infection due to Sphingomonas Paucimobilis, resolved with antibiotics
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Graft versus host disease
    Additional description: 3 GvHD events of GI system (Diarrhoea and vomiting after BMT, due to graft versus host disease. Resolved with use of steroids)
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Viraemia
    Additional description: 3 events of CMV viraemia requiring iv anti-viral therapy, which resolved. 1 event of Adenoviraemia.
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Fever
    Additional description: 3 events of fevers needing admission and antibiotics.
         subjects affected / exposed
    3 / 9 (33.33%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Raised CRP
    Additional description: Self resolved raised inflammatory markers, treated with antibiotics.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
    Additional description: Admitted for sepsis and treated with antibiotics. Unrelated to IMP. Resolved.
         subjects affected / exposed
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fungal infection
    Additional description: 1 event of fungal chest infection pre-IMP infusion requiring lobectomy. 1 event of aspergillosis post BMT (risk factor: pre-BMT aspergilloma), which progressed leading to patient's death. Unrelated to IMP, but immunodeficiency following transplant.
         subjects affected / exposed
    2 / 9 (22.22%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Adverse events RIT phase 1 study
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 9 (0.00%)

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jul 2015
    Notification of updated IMPD (IMPD v2, dated 01/02/2015)
    14 Dec 2016
    •Update the list of co-investigators and collaborators •Facilitate the enrolment process •Clarify the assessment of the dose limiting toxicity •Reduce the number of bloods to be taken after the transplant (HAMA bloods) •Facilitate the infusion of IMP1 and IMP2
    22 Feb 2018
    Notification of trial halt due to unavailability of staff to perform scans at UCLH
    09 Apr 2018
    Notification of trial restart following staffing issues at UCLH for scans being resolved
    04 Nov 2018
    •Amendment seeks approval to change the exclusion criteria from “isolated bone marrow relapse” to just “relapse” in order to allow patients who present with relapses of ALL and AML in other organs to be included in the study. •Changes to scheduled radiation procedures, i.e. skipping dose level 3 of 50MBq/kg and move to dose level 4 of 55MBq/kg for next cohort. •Submission of updated protocol/IB/IMPD: Protocol v5 (26/10/2018), IB v8 (31/03/2018), IMPD v4.1 (30/04/2018)
    09 Sep 2019
    The changes relate to a short extension of the storage of the drug substance, CHX A"-DTPA-anti-CD66 monoclonal antibody.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    22 Feb 2018
    The trial was halted btween February and April 2018, due to unavailability of staff to perform scans (dosimetry) in UCLH. A substantial amendment was submitted as well.
    09 Apr 2018

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The antibody used in this trial expired before the conclusion of the study, so pateints could not be treated at the highest level of radiation foreseen by the protocol. Neverheless suffieient data was collected to demonstrate lack of toxicity.
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA