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    Clinical Trial Results:
    AN OPEN LABEL, PHASE I/II STUDY TO INVESTIGATE THE USE OF VORAXAZE™ AS INTENDED INTERVENTION IN PATIENTS WITH CENTRAL NERVOUS SYSTEM LYMPHOMA AND WITH IMPAIRED RENAL FUNCTION BEING TREATED WITH HIGH-DOSE METHOTREXATE. "VALIDATE"

    Summary
    EudraCT number
    		 2020-004102-63
    Trial protocol
    		 DE  
    Global end of trial date
    01 Oct 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Apr 2026
    First version publication date
    10 Apr 2026
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CNS-Lymphoma-Vorax-1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04841434
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Charité - Universitätsmedizin Berlin
    Sponsor organisation address
    Charitéplatz 1, Berlin, Germany, 10117
    Public contact
    Prof. Dr. Ulrich Keilholz, Charité - Universitätsmedizin Berlin Campus Mitte Charité Comprehensive Cancer Center (CCCC) , +49 (0)30450 564622, CCCC-CTU@charite.de
    Scientific contact
    Prof. Dr. Stefan Schwartz, Campus Benjamin Franklin Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie, +49 (0)30450 564222, CCCC-CTU@charite.de
    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
    20 Nov 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Oct 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Oct 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate tolerability of intended intervention with VoraxazeTM, in addition to LV, in patients with renal impairment or renal failure during previous HD-MTX therapy. • To measure the efficacy of VoraxazeTM in lowering the MTX blood levels in patients who are being treated with HD-MTX and LV. • To demonstrate the feasibility and safety of escalating doses of HD-MTX in patients with renal impairment or renal failure by use of intended intervention with VoraxazeTM, in addition to LV. • To assess the immunological response to VoraxazeTM after repeated use and the effect of any response on the safety and efficacy of VoraxazeTM. • To describe levels of MTX and DAMPA in plasma (and CSF in selected patients) following VoraxazeTM administration. • To assess tolerability of HD-MTX in patients with renal impairment or renal failure in the setting of VoraxazeTM administration. .. and further items as outlined in the protocol.
    Protection of trial subjects
    The study was conducted in accordance with the ICH E6 (R2) Guideline for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, German Medicinal Products Act - AMG), and accordance the latest version of Declaration of Helsinki.
    Background therapy
    		 HDMTX is a key component of treatment protocols for CNSL patients (pts), but impaired renal function in elderly or comorbid pts limits its use. The recombinant enzyme glucarpidase rapidly hydrolyzes MTX into non-toxic metabolites and is approved for therapeutic use in pts with delayed MTX elimination following HDMTX. We conducted a phase I/II study to assess the efficacy of prophylactic glucarpidase in HDMTX-treated pts with renal impairment or a history of delayed MTX elimination. MTX is used either alone or as part of a combined chemotherapy protocol either in standard or high doses in the treatment of a range of cancers and other diseases. Dose escalation were be performed using three dose levels of MTX. This phase I-II trial is intented to demonstrate tolerability (i.e. absence of severe non-hematological toxicity) and efficacy of intended intervention with repeated doses of Voraxaze, in addition to leucovorin (LV), in patients with renal impairment or renal failure during previous HD-MTX therapy.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Aug 2021
    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
    Germany: 18
    Worldwide total number of subjects
    18
    EEA total number of subjects
    18
    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)
    1
    From 65 to 84 years
    15
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted between August 6, 2021 and October 1, 2024 at one site in Germany.

    Pre-assignment
    Screening details
    		 Adult patients with CNS lymphomas who were undergoing active treatment were identified on the basis of the treatment records of our university hospital in accordance with the predefined inclusion criteria. The multidisciplinary lymphoma tumor board at Charité discussed the potential suitability for inclusion in the study on a consensus basis.

    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    The study was designed as a single-arm, open-label, prospective, monocenter, phase I/II study. VoraxazeTM used as intended intervention in patients with CNS lymphoma being treated with HD-MTX who have impaired renal function.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MTX Level 1
    Arm description
    		 3.0 g/m2 Methotrexat + Glucarpidase (IMP)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Glucarpidase
    Investigational medicinal product code
    Voraxaze
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    -Glucarpidase was administered intravenously by bolus intravenous injection over 5 minutes at each cycle 24 hours after start of HD-MTX and Rituximab allowed as standard-of-care for patients. -VoraxazeTM: 2000 Units in patients weighing ≤100kg and at least 20 Units per kg body weight in patients weighing >100kg is given in each HD-MTX cycle as a slow IV injection at 24 hours (+/- 2 hours) after the start of HD-MTX infusion. - Patients were be treated at 3.0 g/m2 dose HD.MTX by injection, with 14 days between cycles (a maximum delay of 28 days is permitted in order to allow time for a patient to recover from the previous cycle). HD-MTX administered over 4 hours according to dose level, given every 14 days for up to 6 cycles.

    Arm title
    		 MTX Level 2
    Arm description
    		 3.5 g/m2 Methotrexat + Glucarpidase (IMP)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Glucarpidase
    Investigational medicinal product code
    Voraxaze
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    -Glucarpidase was administered intravenously by bolus intravenous injection over 5 minutes at each cycle 24 hours after start of HD-MTX and Rituximab allowed as standard-of-care for patients. -VoraxazeTM: 2000 Units in patients weighing ≤100kg and at least 20 Units per kg body weight in patients weighing >100kg is given in each HD-MTX cycle as a slow IV injection at 24 hours (+/- 2 hours) after the start of HD-MTX infusion. - Patients were be treated at 3.5 g/m2 dose HD.MTX by injection, with 14 days between cycles (a maximum delay of 28 days is permitted in order to allow time for a patient to recover from the previous cycle). HD-MTX administered over 4 hours according to dose level, given every 14 days for up to 6 cycles.

    Arm title
    		 MTX Level 3
    Arm description
    		 4.0 g/m2 Methotrexat + Glucarpidase (IMP)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Glucarpidase
    Investigational medicinal product code
    Voraxaze
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    -Glucarpidase was administered intravenously by bolus intravenous injection over 5 minutes at each cycle 24 hours after start of HD-MTX and Rituximab allowed as standard-of-care for patients. -VoraxazeTM: 2000 Units in patients weighing ≤100kg and at least 20 Units per kg body weight in patients weighing >100kg is given in each HD-MTX cycle as a slow IV injection at 24 hours (+/- 2 hours) after the start of HD-MTX infusion. - Patients were be treated at 4.0 g/m2 dose HD.MTX by injection, with 14 days between cycles (a maximum delay of 28 days is permitted in order to allow time for a patient to recover from the previous cycle). HD-MTX administered over 4 hours according to dose level, given every 14 days for up to 6 cycles.

    Number of subjects in period 1
    		MTX Level 1 MTX Level 2 MTX Level 3
    Started
    6
    6
    6
    Completed
    6
    6
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MTX Level 1
    Reporting group description
    		 3.0 g/m2 Methotrexat + Glucarpidase (IMP)

    Reporting group title
    MTX Level 2
    Reporting group description
    		 3.5 g/m2 Methotrexat + Glucarpidase (IMP)

    Reporting group title
    MTX Level 3
    Reporting group description
    		 4.0 g/m2 Methotrexat + Glucarpidase (IMP)

    Reporting group values
    		 MTX Level 1 MTX Level 2 MTX Level 3 Total
    Number of subjects
    		 6 6 6 18
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 0 0 1 1
        From 65-84 years
    		 5 5 5 15
        85 years and over
    		 1 1 0 2
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 76.5 ( 7.01 ) 79.00 ( 5.32 ) 74.33 ( 6.02 ) -
    Gender categorical
    Units: Subjects
        Female
    		 3 3 1 7
        Male
    		 3 3 5 11
    CNS lymphoma type
    PCNSL= Primary central nervous system lymphoma SCNSL =Secondary CNS lymphoma
    Units: Subjects
        PCNSL
    		 5 5 6 16
        SCNSL
    		 1 1 0 2
    ECOG at baseline
    Units: Subjects
        ECOG = 0
    		 0 0 1 1
        ECOG = 1
    		 2 3 1 6
        ECOG = 2
    		 1 1 1 3
        ECOG = 3
    		 0 1 1 2
        ECOG = 4
    		 3 1 2 6
    GFR at baseline
    Units: ml/min/ 1,73 m2
        arithmetic mean (standard deviation)
    		 75.67 ( 7.89 ) 66.5 ( 7.72 ) 64.17 ( 13.13 ) -
    Hemoglobin
    Units: g/dl
        arithmetic mean (standard deviation)
    		 11.41 ( 2.94 ) 11.68 ( 1.32 ) 11.3 ( 0.84 ) -

    End points

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    End points reporting groups
    Reporting group title
    MTX Level 1
    Reporting group description
    		 3.0 g/m2 Methotrexat + Glucarpidase (IMP)

    Reporting group title
    MTX Level 2
    Reporting group description
    		 3.5 g/m2 Methotrexat + Glucarpidase (IMP)

    Reporting group title
    MTX Level 3
    Reporting group description
    		 4.0 g/m2 Methotrexat + Glucarpidase (IMP)

    Primary: Reduction of MTX plasma levels

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    End point title
    		 Reduction of MTX plasma levels [1]
    End point description
    Administration of glucarpidase resulted in a median reduction of MTX plasma levels within 15 minutes by 99.2% (95% CI: 98.4-99.1%). Results from serum samples analyses for anti-glucarpidase antibodies were performed, but in pts with more than two HDMTX cycles, there was no statistically significant difference in the reduction of MTX plasma levels between the first and last cycles (p=0.47). Glucarpidase treatment reduced MTX plasma levels to a median of 0.05 µmol/L (range 0.00-0.84) within 15 minutes. MTX plasma levels remained consistently below 0.6 µmol/L across all cycles at 42 hours or later after start of the HDMTX infusion.
    End point type
    Primary
    End point timeframe
    within 15 minutes
    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: Only descriptive analysis was conducted. Administration of glucarpidase resulted in a median reduction of MTX plasma levels within 15 minutes according to study protocol by 99.2% (95% CI: 98.4-99.1%). MTX plasma levels remained below 0.6 µmol/L across all cycles.
    End point values
    		 MTX Level 1 MTX Level 2 MTX Level 3
    Number of subjects analysed
    6
    6
    6
    Units: µmol/L
    arithmetic mean (standard deviation)
        Cycle 1
    0.9912 ( 0.006 )
    0.9909 ( 0.002 )
    0.9942 ( 0.002 )
        Cycle 2
    0.9860 ( 0.008 )
    0.9942 ( 0.004 )
    0.9930 ( 0.005 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    overall time
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    5.0
    Reporting groups
    Reporting group title
    MTX Level 1
    Reporting group description
    		 3.0 g/m2 Methotrexat + Glucarpidase

    Reporting group title
    MTX Level 2
    Reporting group description
    		 3.5 g/m2 Methotrexat+ Glucarpidase

    Reporting group title
    MTX Level 3
    Reporting group description
    		 4.0 g/m2 Methotrexat+ Glucarpidase

    Serious adverse events
    		 MTX Level 1 MTX Level 2 MTX Level 3
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 6 (83.33%)
    3 / 6 (50.00%)
    4 / 6 (66.67%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Ventricular fibrillation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal hemorrhage
    Additional description: upper and lower
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Lung infection
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 MTX Level 1 MTX Level 2 MTX Level 3
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    General disorders and administration site conditions
    Port dislocation
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Edema limbs
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    3
    2
    0
    Fever
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
         occurrences all number
    2
    1
    1
    Pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Chills
    Additional description: shivering
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Immune system disorders
    allergic reaction
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    4
    2
    0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Intermittand confusional state
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    increased creatinine
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 6 (66.67%)
    2 / 6 (33.33%)
         occurrences all number
    2
    4
    2
    decreased folic acid
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    1
    Loss of weight
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Thrombocyte cell count decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Lack of vitamin D3
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Tachyarrhythmia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Cerebral ischaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Syncope
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Seizure
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anemia
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
         occurrences all number
    7
    2
    2
    Eye disorders
    Glaucomatocyclitic crises
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Diarrhoea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Mucositis
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    0
    Skin and subcutaneous tissue disorders
    Rash
    Additional description: Exanthem
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    Hematuria
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Hypopituitarism
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    4 / 6 (66.67%)
    2 / 6 (33.33%)
    4 / 6 (66.67%)
         occurrences all number
    11
    3
    8
    Covid-19/ Lung infection
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    1
    Bacteraemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Enteritis infectious
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    2 / 6 (33.33%)
         occurrences all number
    1
    2
    3
    Hyperuricaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Aug 2022
    update Protocol Version 3.0 (dated 29/03/2021) to Protocol Version 4.0 (15/02/2022): - Replacement of the investigator's brochure with product information following approval of Voraxaze in the EU - Adjustment of concomitant medication from cycle 2 onwards. (Due to previous IMP-associated AEs, mandatory premedication prior to glucarpidase administration was introduced.) - Adjustment of benefit/risk assessment - Addition of information on adverse events of special interest (AESI)
    18 Sep 2023
    change: Extension of the shelf life of the medication by 1 year
    23 Jul 2024
    update Protocol Version 5.0 (03/05/2024): - Deletion of the follow-up periods 90 and 180 days after the last administration of Voraxaze TM. Now only 30 days follow-up after the last administration.

    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.
    The small sample size, the single-arm design, and a severely ill CNS lymphoma population limit conclusions to the pharmacological efficacy and tolerability of the IMP without meaningful results about the antineoplastic efficacy.
    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.

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