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   43861   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

    Download PDF

    Clinical Trial Results:
    Phase II study on the feasibility and efficacy of R-DHAP + HD-MTX, combined with intrathecal rituximab, followed by autologous stem cell transplantation in patients with a recurrent aggressive B-cell lymphoma with CNS localisation

    Summary
    EudraCT number
    		 2006-002141-37
    Trial protocol
    		 NL  
    Global end of trial date
    17 May 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Dec 2022
    First version publication date
    16 Dec 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    HOVON 80 NHL
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    HOVON
    Sponsor organisation address
    De Boelelaan 1117, Amsterdam, Netherlands,
    Public contact
    HOVON Data Center, HOVON, hdc@erasmusmc.nl
    Scientific contact
    HOVON Data Center, HOVON, hdc@erasmusmc.nl
    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
    03 Jul 2012
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Apr 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    17 May 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess in a multicenter phase II study of patients with a recurrent or progressive B-cell lymphoma with CNS involvement: The progression-free survival after R-DHAP-MTX + rituximab intrathecally followed by myelo-ablative chemotherapy and autologous peripheral blood stem cell transplantation.
    Protection of trial subjects
    Monitoring and Insurance
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Oct 2006
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 38
    Worldwide total number of subjects
    38
    EEA total number of subjects
    38
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    37
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 All subjects gave written informed consent and were screened according to the inclusion- and exclusion criteria.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Arm 1
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Mabthera
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intraventricular use
    Dosage and administration details
    375mg/m2 on day 5. Additionally 10mg i.t./i.ventr.: Cycle 1; day -1, 4, 8, 11, 21. Cycle 2; day -1, 5, 11, 21. Cycle 3; day -1, 11, 25

    Investigational medicinal product name
    Cisplatine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100mg/m2, 24 hrs continuous infusion on day 1.

    Investigational medicinal product name
    Methotrexate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    3000mg/m2, 1 hr infusion on day 15.

    Investigational medicinal product name
    Cytarabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    2g/m2 q 12 hrs (2 doses), 3 hrs infusion for every adminisation of 2g/m2 on day 2.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion, Tablet
    Routes of administration
    Oral use, Intravenous use, Intraventricular use
    Dosage and administration details
    40mg/day, oral/i.v. on day 1, 2, 3, 4. Additionally 4mg i.t./i.ventr: Cycle 1; day -1, 4, 8, 11, 21. Cycle 2; day -1, 5, 11, 21. Cycle 3; day -1, 11, 25.

    Number of subjects in period 1
    		Arm 1
    Started
    38
    Completed
    13
    Not completed
    25
         Adverse reactions
    7
         Other
    8
         Lack of efficacy
    10

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 38 38
    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)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 37 37
        From 65-84 years
    		 1 1
        85 years and over
    		 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 57 (23 to 65) -
    Gender categorical
    Units: Subjects
        Female
    		 17 17
        Male
    		 21 21

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm 1
    Reporting group description
    		 -

    Primary: Primary Endpoint

    		 Close Top of page
    End point title
    		 Primary Endpoint [1]
    End point description
    End point type
    Primary
    End point timeframe
    See publication.
    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: See attached chart/documents for results.
    End point values
    		 Arm 1
    Number of subjects analysed
    36
    Units: Whole
    36
    Attachments
    		 Statistical data section from publication
    List of reported non-SAE's
    List of reported SAE's
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Please refer to Adverse event reporting additional description.
    Adverse event reporting additional description
    All adverse events of Grade 2 or higher, except progression of disease, occurring during the protocol treatment period will be reported. Adverse events occurring after that period should also be reported if considered related to protocol treatment. Follow up of ongoing adverse events ends at day 30 following the last dose of protocol treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    3
    Reporting groups
    Reporting group title
    Experimental Group
    Reporting group description
    		 -

    Serious adverse events
    		 Experimental Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 36 (55.56%)
         number of deaths (all causes)
    30
         number of deaths resulting from adverse events
    Vascular disorders
    Vascular disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    General disorders and administration site conditions
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    4 / 36 (11.11%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 3
    Immune system disorders
    Immune system disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory, thoracic and mediastinal disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Psychiatric disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Investigations
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Nervous system disorders
    Nervous system disorder
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    4 / 36 (11.11%)
         occurrences causally related to treatment / all
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    4 / 36 (11.11%)
         occurrences causally related to treatment / all
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Hepatobiliary disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Infections and infestations
    Additional description: All combined, see SAE chart for details.
         subjects affected / exposed
    7 / 36 (19.44%)
         occurrences causally related to treatment / all
    4 / 10
         deaths causally related to treatment / all
    1 / 4
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Experimental Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    35 / 36 (97.22%)
    Vascular disorders
    Vascular
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    7 / 36 (19.44%)
         occurrences all number
    8
    General disorders and administration site conditions
    Constitutional symptoms
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    12 / 36 (33.33%)
         occurrences all number
    14
    Pain
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    11 / 36 (30.56%)
         occurrences all number
    13
    Respiratory, thoracic and mediastinal disorders
    Pulmonary/upper respiratory
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences all number
    2
    Cardiac disorders
    Cardiac general
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    7 / 36 (19.44%)
         occurrences all number
    8
    Nervous system disorders
    Neurology
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    14 / 36 (38.89%)
         occurrences all number
    30
    Blood and lymphatic system disorders
    Blood/bone marrow
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences all number
    3
    Coagulation
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences all number
    3
    Hemorrhage/bleeding
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences all number
    4
    Lymphatics
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences all number
    3
    Ear and labyrinth disorders
    Auditory/ear
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences all number
    2
    Eye disorders
    Ocular/visual
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences all number
    3
    Gastrointestinal disorders
    Gastrointestinal
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    19 / 36 (52.78%)
         occurrences all number
    50
    Hepatobiliary disorders
    Hepatobiliary/pancreas
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    1 / 36 (2.78%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Dermatology/skin
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    4 / 36 (11.11%)
         occurrences all number
    4
    Renal and urinary disorders
    Renal/genitourinary
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    2 / 36 (5.56%)
         occurrences all number
    3
    Endocrine disorders
    Endocrine
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    3 / 36 (8.33%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Musculoskeletal/soft tissue
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    5 / 36 (13.89%)
         occurrences all number
    5
    Infections and infestations
    Infection
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    26 / 36 (72.22%)
         occurrences all number
    64
    Metabolism and nutrition disorders
    Metabolic/laboratory
    Additional description: All combined, see non-SAE chart for details.
         subjects affected / exposed
    25 / 36 (69.44%)
         occurrences all number
    62

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Dec 2008
    • p1,6: Telephone numbers and names statistician and datamanger changed • p14: In table 4 mg dose/day dexamethasone added to rituximab i.t. • p14: Rituximab i.t./i.ventr. diluted in NaCl to a concentration of 5 mg/ml in stead of 10 mg/ml • p16: Addition of dexamethasone and dilution of rituximab as indicated on p14 • p16: Addition of anti-histaminics to premedication before every i.t. treatment
    02 Jun 2009
    • p10: Addition of text: However, in a number of patients a temporary painful lumbosacral radiculopathy occurred after lumbar administration of 25 mg. Therefore the intrathecal dose will be limited to 10 mg.’ • p14: In table first row deleted, in second row day –1 added to cycle 1 • p16: Dose escalation i.t. rituximab to 25 mg deleted dose will be continued at 10 mg

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Fri Apr 26 01:37:15 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA