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    Clinical Trial Results:
    A Randomized, Controlled, Open-Label Phase 3 Study of Melflufen in combination with Daratumumab Compared with Daratumumab in Patients with Relapsed or Relapsed-Refractory Multiple Myeloma

    Summary
    EudraCT number
    		 2019-002161-36
    Trial protocol
    		 CZ   NO   HU   FI   SK   BG   PL   GR   ES  
    Global end of trial date
    07 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Apr 2023
    First version publication date
    07 Apr 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    OP-108
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04649060
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Oncopeptides AB
    Sponsor organisation address
    Luntmakargatan 46, Stockholm, Sweden, SE-117 37
    Public contact
    Clinical Trials Information Desk, Oncopeptides AB, trials@oncopeptides.com
    Scientific contact
    Clinical Trials Information Desk, Oncopeptides AB, trials@oncopeptides.com
    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
    07 Feb 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Feb 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To show superiority of progression free-survival (PFS) in patients treated with melflufen and dexamethasone in combination with daratumumab compared to daratumumab alone.
    Protection of trial subjects
    This clinical study was designed, implemented, and reported in accordance with the International Conference of Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations, and with the ethical principles laid down in the Declaration of Helsinki. Eligible patients were only to be included in the study after providing written, IEC-approved informed consent. The clinical study was designed based on well-established guidance for oncology studies including RRMM management, response assessment, and National Comprehensive Cancer Network Guidelines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Dec 2020
    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
    Norway: 6
    Country: Number of subjects enrolled
    Poland: 12
    Country: Number of subjects enrolled
    Bulgaria: 3
    Country: Number of subjects enrolled
    Czechia: 18
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Georgia: 1
    Country: Number of subjects enrolled
    Serbia: 7
    Country: Number of subjects enrolled
    Ukraine: 6
    Worldwide total number of subjects
    54
    EEA total number of subjects
    40
    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)
    20
    From 65 to 84 years
    34
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 54 patients were enrolled in the Study, 27 in Arm A and 27 in Arm B. Among the enrolled patients, 22 in Arm A and 26 in Arm B received at least one dose of study drug.

    Pre-assignment
    Screening details
    		 Key inclusion criteria: age ≥ 18 years; prior diagnosis of multiple myeloma; double refractory to an immunomodulatory drug and a proteasome Inhibitor or received at least 3 prior lines of therapy; measurable disease; life expectancy of ≥ 6 months; ECOG performance ≤ 2; QT interval ≤470 msec; adequate organ function based on lab results.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Independent Review Committee was planned to be blinded to treatment assignment. Due to the early termination, the response assessments were only done by Investigators, not by an Independent Review Committee (IRC). No IRC meeting had yet been held.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A
    Arm description
    		 Patients in Arm A received treatment with melflufen, dexamethasone, and daratumumab in 28-day cycles until disease progression, unacceptable toxicity, patient withdrawal of consent, or the treating physician determined it was no longer in the patient’s best interest to continue the treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Melflufen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate and solution for solution for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    In each 28-day cycle, melflufen 30 mg was given as a 30-minute intravenous infusion on Day 1.

    Investigational medicinal product name
    Dexamethasone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    In each 28-day cycle, dexamethasone 40 mg was given per oral weekly. For patients ≥ 75 years, dexamethasone 20 mg was given per oral weekly.

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    Darzalex FASPRO
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Daratumumab 1800 mg was given subcutaneously on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7.

    Arm title
    		 Arm B
    Arm description
    		 Patients in Arm B received treatment with daratumumab in 28-day cycles until disease progression, unacceptable toxicity, patient withdrawal of consent, or the treating physician determined it was no longer in the patient’s best interest to continue the treatment. Patients in Arm B with a confirmed disease progression had the option to cross over and receive the same treatment as in Arm A. There were 2 patients in Arm B that crossed over and received the same treatment as in Arm A after a confirmed disease progression and received at least one dose of treatment. For the 2 crossover patients, 1 was discontinued due to adverse events, and 1 was lost to follow-up.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Daratumumab
    Investigational medicinal product code
    Other name
    Darzalex FASPRO
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Daratumumab 1800 mg was given subcutaneously on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7.

    Number of subjects in period 1
    		Arm A Arm B
    Started
    27
    27
    Treated
    22
    26
    Completed
    0
    0
    Not completed
    27
    27
         Physician decision
    1
    1
         Patient request
    1
    -
         Unknown
    1
    -
         Study terminated by sponsor
    17
    10
         Adverse event
    -
    3
         Progressive disease
    3
    12
         Failed criteria for treatment initiation
    4
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients in Arm A received treatment with melflufen, dexamethasone, and daratumumab in 28-day cycles until disease progression, unacceptable toxicity, patient withdrawal of consent, or the treating physician determined it was no longer in the patient’s best interest to continue the treatment.

    Reporting group title
    Arm B
    Reporting group description
    		 Patients in Arm B received treatment with daratumumab in 28-day cycles until disease progression, unacceptable toxicity, patient withdrawal of consent, or the treating physician determined it was no longer in the patient’s best interest to continue the treatment. Patients in Arm B with a confirmed disease progression had the option to cross over and receive the same treatment as in Arm A. There were 2 patients in Arm B that crossed over and received the same treatment as in Arm A after a confirmed disease progression and received at least one dose of treatment. For the 2 crossover patients, 1 was discontinued due to adverse events, and 1 was lost to follow-up.

    Reporting group values
    		 Arm A Arm B Total
    Number of subjects
    		 27 27 54
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 12 8 20
        From 65-75 years
    		 13 16 29
        Over 75 years
    		 2 3 5
    Age continuous
    Units: years
        median (full range (min-max))
    		 65 (43 to 80) 68 (50 to 83) -
    Gender categorical
    Units: Subjects
        Female
    		 11 10 21
        Male
    		 16 17 33
    Race
    Units: Subjects
        White
    		 27 27 54
    Ethnicity
    Units: Subjects
        Not Hispanic or Latino
    		 27 27 54
    Baseline Eastern Cooperative Oncology Group (ECOG)
    Units: Subjects
        score = 0
    		 8 6 14
        score = 1
    		 18 15 33
        score = 2
    		 1 6 7
    Weight
    Units: kg
        median (full range (min-max))
    		 78.0 (61.0 to 103.8) 76.0 (56.3 to 107.6) -
    Height
    Units: cm
        median (full range (min-max))
    		 168 (151 to 195) 167 (150 to 188) -

    End points

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    End points reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Patients in Arm A received treatment with melflufen, dexamethasone, and daratumumab in 28-day cycles until disease progression, unacceptable toxicity, patient withdrawal of consent, or the treating physician determined it was no longer in the patient’s best interest to continue the treatment.

    Reporting group title
    Arm B
    Reporting group description
    		 Patients in Arm B received treatment with daratumumab in 28-day cycles until disease progression, unacceptable toxicity, patient withdrawal of consent, or the treating physician determined it was no longer in the patient’s best interest to continue the treatment. Patients in Arm B with a confirmed disease progression had the option to cross over and receive the same treatment as in Arm A. There were 2 patients in Arm B that crossed over and received the same treatment as in Arm A after a confirmed disease progression and received at least one dose of treatment. For the 2 crossover patients, 1 was discontinued due to adverse events, and 1 was lost to follow-up.

    Primary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    To show the superiority of PFS in patients treated with melflufen and dexamethasone in combination with daratumumab compared to daratumumab alone. PFS is defined as the duration in months from the date of randomization to the date of first documentation of confirmed progressive disease or death due to any cause.
    End point type
    Primary
    End point timeframe
    From the date of randomization until the end of study.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    27 [1]
    27 [2]
    Units: Events (disease progression/death)
    3
    13
    Notes
    [1] - Disease progression/death was reported in 3 patients. The median PFS was not reached in Arm A.
    [2] - Disease progression/death was reported in 13 patients. The median PFS was 4.9 months in Arm B.
    Statistical analysis title
    		 Statistical Analysis for PFS
    Statistical analysis description
    The primary statistical analysis of PFS was performed using a Log-rank test. The Cox proportional hazard was used to estimate the hazard ratio for melflufen+dexamethasone+daratumumab versus daratumumab and its 95% confidence interval.
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0032
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.05
         upper limit
    		 0.65

    Secondary: Overall Response Rate (ORR)

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    End point title
    		 Overall Response Rate (ORR)
    End point description
    To evaluate and compare ORR in patients treated with melflufen and dexamethasone in combination with daratumumab compared to daratumumab alone. ORR is the proportion of patients who achieve a best-confirmed response of stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR).
    End point type
    Secondary
    End point timeframe
    From the date of randomization until the end of study.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    27
    27
    Units: percent
        number (confidence interval 95%)
    59.3 (38.8 to 77.6)
    29.6 (13.8 to 50.2)
    Statistical analysis title
    		 Statistical Analysis for ORR
    Statistical analysis description
    ORR was presented together with two-sided 95% exact binomial confidence intervals based on the Clopper-Pearson method. The treatment groups were compared using the Cochran-Mantel-Haenszel test.
    Comparison groups
    Arm A v Arm B
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.03
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Best Response

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    End point title
    		 Best Response
    End point description
    To evaluate the best response in patients treated with melflufen and dexamethasone in combination with daratumumab compared to daratumumab alone.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until the end of study.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    27
    27
    Units: number of patient
        Complete Response (CR)
    1
    0
        Very Good Partial Response (VGPR)
    4
    3
        Partial Response (PR)
    11
    5
        Minimal Response (MR)
    3
    5
        Stable Disease (SD)
    3
    5
        Progressive Disease (PD)
    1
    5
        Not Evaluable (NE)
    4
    4
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    To evaluate the OS in patients treated with melflufen and dexamethasone in combination with daratumumab compared to daratumumab alone. OS is defined as time in months from the date of randomization to death due to any cause.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until the end of study.
    End point values
    		 Arm A Arm B
    Number of subjects analysed
    27 [3]
    27 [4]
    Units: death
    2
    4
    Notes
    [3] - The median OS was 11.0 months in Arm A.
    [4] - The 4 deaths include 1 death in the crossover group. The median OS was not reached in Arm B.
    Statistical analysis title
    		 Statistical Analysis for OS
    Statistical analysis description
    OS was performed using Kaplan-Meier method. The median time to event was estimated for each treatment arm from the 50th percentile of the corresponding Kaplan-Meier estimates. 95% confidence intervals were based on the log(-log(survival)) distribution.
    Comparison groups
    Arm B v Arm A
    Number of subjects included in analysis
    54
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.37
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.086
         upper limit
    		 2.57

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs: from the start of study treatment until 30 days after the last dose of study drug or initiation of subsequent therapy. SAEs: from signing of the ICF until 30 days after the last dose of study drug or initiation of subsequent therapy.
    Adverse event reporting additional description
    Non-serious AEs were not calculated in this study. The data reported in the non-serious AE section include all AEs (non-serious AEs and SAEs).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Arm A
    Reporting group description
    		 Safety was evaluated based on the safety analysis set, which included all patients that had received at least 1 dose of melflufen, dexamethasone, or daratumumab. There were 22 patients in Arm A who received at least 1 dose of study treatment.

    Reporting group title
    Arm B
    Reporting group description
    		 Safety was evaluated based on the safety analysis set, which included all patients that had received at least 1 dose of melflufen, dexamethasone, or daratumumab. There were 26 patients in Arm B who received at least 1 dose of study treatment.

    Reporting group title
    Crossover
    Reporting group description
    		 Safety was evaluated based on the safety analysis set, which included all patients that had received at least 1 dose of melflufen, dexamethasone, or daratumumab. There were 2 patients who crossed over from Arm B to receive the same treatment as in Arm A after a confirmed disease progression and received at least 1 dose of study treatment.

    Serious adverse events
    		 Arm A Arm B Crossover
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 22 (27.27%)
    12 / 26 (46.15%)
    1 / 2 (50.00%)
         number of deaths (all causes)
    2
    3
    1
         number of deaths resulting from adverse events
    0
    1
    1
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 26 (7.69%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (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
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 26 (11.54%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 26 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (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
    Gastrointestinal disorders
    Enterocolitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 26 (0.00%)
    0 / 2 (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
    Gingival bleeding
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (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
    Rectal haemorrhage
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 26 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (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
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 26 (7.69%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Asymptomatic COVID-19
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (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
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 26 (3.85%)
    0 / 2 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A Arm B Crossover
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    21 / 22 (95.45%)
    22 / 26 (84.62%)
    2 / 2 (100.00%)
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 26 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    7
    0
    0
    Platelet count decreased
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences all number
    9
    1
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 26 (7.69%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 26 (7.69%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    0
    Nervous system disorders
    Polyneuropathy
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 26 (7.69%)
    0 / 2 (0.00%)
         occurrences all number
    2
    2
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    13 / 22 (59.09%)
    8 / 26 (30.77%)
    1 / 2 (50.00%)
         occurrences all number
    78
    14
    8
    Anaemia
         subjects affected / exposed
    12 / 22 (54.55%)
    7 / 26 (26.92%)
    1 / 2 (50.00%)
         occurrences all number
    37
    23
    5
    Thrombocytopenia
         subjects affected / exposed
    12 / 22 (54.55%)
    4 / 26 (15.38%)
    0 / 2 (0.00%)
         occurrences all number
    65
    15
    0
    Lymphopenia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 26 (7.69%)
    0 / 2 (0.00%)
         occurrences all number
    10
    4
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 26 (11.54%)
    0 / 2 (0.00%)
         occurrences all number
    2
    3
    0
    Fatigue
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 26 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences all number
    4
    1
    0
    Nausea
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 26 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    2
    0
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 26 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    2
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 26 (11.54%)
    1 / 2 (50.00%)
         occurrences all number
    2
    3
    1
    Infection
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 26 (7.69%)
    0 / 2 (0.00%)
         occurrences all number
    4
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 26 (3.85%)
    0 / 2 (0.00%)
         occurrences all number
    3
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 26 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Sep 2020
    The overall rationale for Amendment 1 was an update of the study design to 1:1 randomization and increased sample size to 240 patients with 90% power at the request of Competent Authorities. Also, a crossover opportunity was added to allow patients with documented disease progression in Arm B to receive melflufen, dexamethasone, and daratumumab treatment. In addition, exclusion criteria related to infections were updated with information about COVID-19. Information that the subcutaneous formulation of daratumumab used in the study has been approved by FDA in the US, EMA in Europe, and MHRA in UK during 2020 was added.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    08 Jul 2021
    The study was prematurely terminated as a consequence of the financial situation of the Sponsor following the partial clinical hold put on the melflufen program by the FDA. Enrollment was stopped on 08-Jul-2021, and the decision to prematurely close the Study was taken on 04-Nov-2021.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated prematurely with limited data available, and data cleaning was not done according to the original plan. Due to the early termination, the response assessments were only done by Investigators. No IRC meeting had yet been held.
    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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