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    Summary
    EudraCT Number:2019-004604-35
    Sponsor's Protocol Code Number:ICONMM
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-06-03
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2019-004604-35
    A.3Full title of the trial
    A phase 2 study of CC220 (iberdomide) combined with low-dose cyclophosphamide and dexamethasone in relapsed/refractory multiple myeloma (IberCd): ICON study

    Een fase 2 studie van iberdomide gecombineerd met cyclofosfamide en dexamethason in patiënten met een recidief of refractair Multipel Myeloom (MM)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Iberdomide combined with low-dose cyclophosphamide and dexamethasone in relapsed/refractory multiple myeloma
    Iberdomide gecombineerd met cyclofosfamide en dexamethason in patiënten met een recidief of refractair Multipel Myeloom
    A.3.2Name or abbreviated title of the trial where available
    ICON study
    ICON studie
    A.4.1Sponsor's protocol code numberICONMM
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorVU University Medical Center
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCelgene B.V.
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmsterdam UMC, location VUmc
    B.5.2Functional name of contact pointTrial office dept. of Hematology
    B.5.3 Address:
    B.5.3.1Street AddressDe Boelelaan 1117
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1081 HV
    B.5.3.4CountryNetherlands
    B.5.4Telephone number0031204442604
    B.5.6E-mailhemtrial@vumc.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIberdomide
    D.3.2Product code CC-220
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIberdomide
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.3Other descriptive nameCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.6
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeIMID/CELMOD. Iberdomide (CC-220) is an orally available agent which binds to the cereblon E3 ligase complex and has multiple effects on cells of the immune system, including B cells and T cells.
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Endoxan
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter BV
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCyclophosphamide
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Dexamethasone
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDexamethason
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDexamethason
    D.3.9.3Other descriptive nameDEXAMETHASONE
    D.3.9.4EV Substance CodeSUB07017MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number20 to 40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIberdomide
    D.3.2Product code CC-220
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIberdomide
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.3Other descriptive nameCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeIMID/CELMOD. Iberdomide (CC-220) is an orally available agent which binds to the cereblon E3 ligase complex and has multiple effects on cells of the immune system, including B cells and T cells.
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIberdomide
    D.3.2Product code CC-220
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIberdomide
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.3Other descriptive nameCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.0
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeIMID/CELMOD. Iberdomide (CC-220) is an orally available agent which binds to the cereblon E3 ligase complex and has multiple effects on cells of the immune system, including B cells and T cells.
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameIberdomide
    D.3.2Product code CC-220
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIberdomide
    D.3.9.1CAS number 1560678-63-8
    D.3.9.2Current sponsor codeCC-220
    D.3.9.3Other descriptive nameCC-220
    D.3.9.4EV Substance CodeSUB179693
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeIMID/CELMOD. Iberdomide (CC-220) is an orally available agent which binds to the cereblon E3 ligase complex and has multiple effects on cells of the immune system, including B cells and T cells.
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed/refractory multiple myeloma
    Recidief of refractair Multipel Myeloom
    E.1.1.1Medical condition in easily understood language
    Relapsed/refractory multiple myeloma
    Patiënten met een recidief of refractair Multipel Myeloom
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The goal of this trial is to investigate the efficacy and safety of the IberCd combination in multiple myeloma patients who have refractory disease or a relapse after prior treatment with lenalidomide.

    Primary objective:
    - To evaluate progression-free survival
    Het doel van dit onderzoek is om de veiligheid en werkzaamheid van de combinatie van iberdomide, cyclofosfamide en dexamethason te onderzoeken bij patiënten met een recidief of refractair Multipel Myeloom.

    Primary objective: progressie vrije overleving
    E.2.2Secondary objectives of the trial
    Secondary objectives:
    - To investigate the efficacy of IberCd, as determined by the (s)CR+VGPR+PR rate according to the international myeloma working group (IMWG) criteria.
    - To evaluate toxicity
    - To evaluate overall survival
    - To evaluate time to response
    - To evaluate duration of response
    - To evaluate Time to Second Objective Disease
    - Progression (PFS2)
    - To evaluate time to next treatment (TTNT)
    - Effectiviteit van IberCD (volgens IMWG criteria)
    - Toxiciteit
    - Overall survival
    - Tijd tot respons
    - Respons duur
    - Tijd tot tweede objectieve ziekte
    - Progressie
    - Tijd tot volgende behandeling
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Age ≥ 18 years.

    2. Subject must have documented diagnosis of multiple myeloma and have measurable disease as defined by any of the following:
    o Serum monoclonal paraprotein (M-protein) level ≥5 g/L (0.5 g/dL); or urine M-protein level ≥200 mg/24 hours; or serum immunoglobulin free light chain ≥100 mg/L (10 mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain ratio (See Appendix A)

    3. Relapsed or refractory disease. Relapse is defined as progression of disease after an initial response to previous treatment, more than 60 days after cessation of treatment. Refractory disease is defined as <50% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment.

    4. Subject had 2-4 prior anti-myeloma regimens.
    (Note: Induction, bone marrow transplant with or without maintenance therapy is
    considered one regimen; Prior pomalidomide is allowed )

    5. Subject has developed lenalidomide-refractory disease (any dose) during prior treatment with lenalidomide or a lenalidomide-containing regimen
    Lenalidomide-refractory MM is defined as progressive disease during therapy, no response (< PR) to prior lenalidomide-containing therapy, or progression within 60 days of discontinuation from lenalidomide-containing regimens, according to the International Myeloma Working Group criteria.

    6. WHO performance 0, 1, or 2

    7. Life expectancy at least 3 months

    8. Written informed consent

    9. A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not
    been naturally postmenopausal (amenorrhea following cancer therapy does not rule out
    childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time
    in the preceding 24 consecutive months) and must:
    a. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
    b. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment
    (including dose interruptions), and for at least 28 days after the last dose of CC-220, 90 days after the last dose of cyclophosphamide, whichever is longer. Contraception requirements are detailed in Appendix H.

    10. Male subjects must:
    a. Practice true abstinence* (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following the last dose of study treatment, even if he has undergone a successful vasectomy.

    * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]

    11. Males must agree to refrain from donating sperm while on study treatment, during dose
    interruptions and for at least 90 days following last dose of study treatment.

    12. All subjects must agree to refrain from donating blood while on study treatment, during
    dose interruptions and for at least 28 days following the last dose of study treatment.

    13. All male and female subjects must follow all requirements defined in the Pregnancy
    Prevention Program (v5.1). See Appendix H for CC-220 Pregnancy Prevention Plan for
    Subjects in Clinical Trials.
    1. 18 jaar en ouder

    2. Deelnemer moet gedocumenteerd MM hebben volgens de criteria en meetbare ziekte gedefinieerd als volgt: serum M proteïne > aan 5g/L (0,5g/dL) of urine M proteïne > 200 mg/24uur of serum immunoglobuline FLC > 100 mg/L (10mg/dL) en abnormaal serum immunoglobuline kappa lambda FLC ratio >100mg/L.

    3. Gerecidiveerde of refractaire ziekte. Recidief is gedefinieerd als progressieve ziekte na initiële respons op eerdere behandeling, meer dan 60 dagen na staken van behandeling. Refractaire ziekte is gedefinieerd als <25% afname van het M proteïne of progressie van ziekte tijdens de behandeling of binnen 60 dagen na staken van de behandeling.

    4. Patiënt heeft tenminste 2-4 eerdere antimyeloom behandelingen gehad.
    (Inductietherapie, beenmergtransplantatie met of zonder onderhoudstherapie wordt beschouwd als 1 behandellijn. Eerdere behandeling met pomalidomide is toegestaan)

    5. Patiënt heeft lenalidomide refractaire ziekte ontwikkelt gedurende voorafgaande behandeling met een lenalidomide bevattende therapie.

    6. WHO performance status 0, 1, of 2

    7. Levensverwachting van tenminste 3 maanden

    8. Geschreven informed consent

    9. Een vrouw die zwanger kan worden, is een vrouw die: 1) op enig moment menarche heeft bereikt
    2) geen hysterectomie (verwijdering baarmoeder) of een dubbelzijdige ovariectomie (verwijdering eierstokken) heeft ondergaan of 3) niet op natuurlijke wijze post-menopauzaal (amenorrhoe na chemotherapie sluit eventuele zwangerschap niet altijd uit) gedurende minstens 24 aaneengesloten maanden (dat wil zeggen heeft een menstruatie gehad gedurende de voorafgaande 24 maanden) en moet:
    - 2 negatieve zwangerschapstesten hebben (gezien door arts/onderzoeker) voor het starten van de behandeling met studiemedicatie en toestemming geven om zwangerschapstesten uit te voeren gedurende de studie en na afloop van de studie ook indien er sprake is van volledige en voortdurende onthouding.
    - Of ermee instemmen om twee adequate verschillende soorten anticonceptie onafgebroken te gebruiken (zeer effectief = IUD, anticonceptie pil, vasectomie partner / effectief = condoom bij partner) vanaf 28 dagen voor start van de studie, gedurende de studie en tot 28 dagen na de laatste dosis iberdomide of 90 dagen na de laatste dosis cyclofosfamide. Of volledige en voortdurende onthouding van heteroseksueel contact (wordt op maandelijkse basis geëvalueerd)


    10. Mannelijke deelnemers moeten instemmen met volledige en voortdurende onthouding of gebruik van een condoom bij seksueel contact (ook diegenen die een vasectomie hebben ondergaan) met een zwangere vrouw of een vrouw die zwanger kan worden, gedurende de gehele duur van de behandeling, tijdens behandelingsonderbreking en 28 dagen (iberdomide) of 90 dagen (cyclofosfamide) na stoppen behandeling.



    11. Mannelijke patiënten mogen geen sperma doneren tijdens de studie en tot 90 dagen na de laatste dosis van de studiebehandeling.

    12. Alle patiënten moeten er mee instemmen geen bloed te doneren tijdens de studie tot en met 28 dagen na de laatste dosis van de studiebehandeling.

    13. Alle mannelijke en vrouwelijke patiënten moeten de instructies opvolgen zoals omschreven in het preventie van zwangerschap programma (appendix H).
    E.4Principal exclusion criteria

    1. Subjects who previously received continuous low-dose cyclophosphamide alone or in combination with other anti-MM agents are excluded (cyclophosphamide once weekly such as in bortezomib-cyclophospahmide-dexametahsone regimen (VCD) is allowed).

    2. Treatment with prior iberdomide

    3. Non-secretory MM

    4. Systemic AL amyloidosis or plasma cell leukemia (>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom’s macroglobulinemia

    5. Subject has known meningeal involvement of multiple myeloma

    6. Inadequate marrow reserve as defined by a platelet count <75 x 109/L or an absolute neutrophil count <1.0 x 109/L

    7. Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L)

    8. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide,
    pomalidomide, dexamethasone, or cyclophosphamide. Subject has known or suspected hypersensitivity to the excipients contained in the formulation of iberdomide, dexamethasone, or cyclophosphamide.

    9. Subject has received any of the following within the last 14 days of initiating IberCd:
    - Plasmapheresis
    - Major surgery (as defined by the Investigator)
    - Radiation therapy other than local therapy for MM associated bone lesions
    - Use of any systemic myeloma drug therapy

    10. Subject has been treated with an investigational agent (ie, an agent not commercially
    available) within 28 days or 5 half-lives (whichever is longer) of initiating IberCd treatment
    11. Subject has current or prior use of immunosuppressive medication within 14 days prior to the first dose of IP. The following are exceptions to this criterion:
    - Intranasal, inhaled, topical or local steroid injections (eg, intra-articular injection)
    - Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or equivalent
    - Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)

    12. Subject has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St.
    John’s Wort or related products within two weeks prior to dosing and during the course
    of study

    13. Creatinine clearance <30 ml /min or requirement of dialysis.

    14. Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure; myocardial infarction within the last 6 months of study entry); unstable angina; unstable cardiac arrhythmias; clinically significant pericardial disease)

    15. Significant hepatic dysfunction (total bilirubin  3 times normal value or transaminases  3 times normal value), unless related to myeloma

    16. Subject has any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, respiratory disease, infection, hypertension, etc.) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.

    17. Subject known to test positive for human immunodeficiency virus (HIV), chronic or
    active hepatitis B, or active hepatitis A or C

    18. Peripheral neuropathy of ≥grade 2.

    19. Subjects with gastrointestinal disease that may significantly alter the absorption of
    CC-220

    20. History of active malignancy during the past 3 years, except squamous cell and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast and incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is cured, or malignancy that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.

    21. Subject is known or suspected of not being able to comply with the study protocol
    (eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments.

    22. Subject is a female who is pregnant, nursing or breastfeeding, or who intends to become
    pregnant during the participation in the study

    23. Subject is unable or unwilling to undergo protocol required thromboembolism
    prophylaxis

    24. Subject has previously received an allogeneic stem cell transplantation within 1 year before the date of registration and has not used immunosuppressive drugs within one month before the date of registration.
    1. Patiënten die eerder een behandeling hebben gehad met continue lage dosis cyclofosfamide alleen of in combinatie met andere anti-MM middelen. (Cyclofosfamide één keer per week zoals bij bortezomib-cyclofosfamide-dexamethason is wel toegestaan).

    2. Eerdere behandeling met Iberdomide

    3. Non-secretoir Multipel Myeloom

    4. Systemische AL amyloidose of plasmacelleukemie (>2.0x109/L circulerende plasma cellen in de differentiatie) of Waldenstrom macroglobulinemie.

    5. Patiënt is bekend met meningeale laesies van het multipel myeloom.

    6. Inadequate beenmerg reserve gedefinieerd als trombocyten <75 x 109/L of absolute neutrofielen aantal <1.0 x 109/L

    7. Gecorrigeerd calcium >13.5 mg/dL (>3.4 mmol/L)

    8. Bekende overgevoeligheid of ernstige allergische dan wel anafylactische reacties voor componenten van thalidomide, lenalidomide, pomalidomide, dexamethason of cyclofosfamide.

    9. Patiënten die 14 dagen voor start van de studiebehandeling (IberCd) plasmaferese, een (grote) operatie of radiotherapie (anders dan als lokale therapie voor een bot laesie) hebben ondergaan of systemische myeloom therapie hebben gehad.

    10. Patiënten die behandeld zijn met een studiebehandeling (i.e. een middel dat niet commercieel beschikbaar is) in de afgelopen 28 dagen of 5 keer de half waarde tijd van de behandeling voor start van huidige studiebehandeling (IberCd).

    11. Patiënten die immunosuppressieve medicatie gebruiken of hebben gebruikt in de afgelopen 14 dagen voor de eerste dosis van de studiebehandeling. De volgende uitzonderingen worden gemaakt:
    -Intra nasale steroïden, inhalatie steroïden, plaatselijke steroïden of lokale steroïde injecties
    -Systemische corticosteroïden tot max 10 mg prednison per dag of een equivalent hiervan
    -Steroïden als premedicatie voor overgevoeligheidsreacties (bijvoorbeeld voor een CT scan)

    12. Patiënten die sterke CYP3A4/5 inhibitors of inducers hebben gebruikt zoals grapefruitsap, Sint Jans Kruid of andere producten in de afgelopen 2 weken voor de eerste dosis én tijdens de studie.
    13. Creatinine klaring <30 ml/min of dialyse behoefte

    14. Aanwezigheid van klinisch significante hart aandoening (NHYA klasse III of IV hartfalen, myocardinfarct in de afgelopen 6 maanden voor start studie, instabiele AP, instabiele aritmieën of pericard ziekten).

    15. Significante leverfunctie stoornis (totaal bilirubine > 3 keer de normaalwaarde of transaminases > 3 keer de normaalwaarde, tenzij gerelateerd aan myeloom.

    16. Elke gelijktijdige optredende ernstige en/of oncontroleerbare medische toestand (bijvoorbeeld diabetes, longziekten, infecties of hypertensie) die waarschijnlijk gaat interfereren met studieprocedures of resultaten, of die volgens de onderzoeker gevaar gaat opleveren bij deelname aan deze studie.

    17. Bekende seropositiviteit voor HIV, actieve of chronische hepatitis B infectie of actieve hepatitis A of C infectie.

    18. Perifere neuropathie > graad 2

    19. Patiënten met een gastro-intestinale ziekte mogelijk leidend tot een verminderde opname van iberdomide.

    20. Een maligniteit in de voorgeschiedenis in de afgelopen 3 jaar (met uitzondering van plaveiselcel- en basaalcelcarcinoom van de huid of carcinoma in situ van de cervix of borst en T1a of T1b prostaatcarcinoom dan wel een behandeld prostaat carcinoom) of een maligniteit die volgens de lokale onderzoeker en ook de hoofdonderzoeker wordt beschouwd als genezen met minimaal risico op recidief binnen 3 jaar.

    21. Patiënten waarvan bekend is, of waarvan de verwachting is dat ze niet in staat zijn te voldoen aan de studie eisen (bijvoorbeeld alcoholisme, drugsverslaving of psychiatrische afwijkingen) of de patiënt is en een zodanige toestand, dat naar mening van de onderzoeker deelname niet in het belang van de patiënt is of die de protocol specifieke evaluatie beperkt, verhindert of beïnvloedt.

    22. Zwangere vrouwen, vrouwen die borstvoeding geven of vrouwen die zwanger willen worden gedurende deelname aan de studie.

    23. Patiënten die tromboseprofylaxe (conform protocol) niet kunnen of willen gebruiken.

    24. Allogene stamceltransplantatie (< 1 jaar voor studie registratie) en geen gebruik van immunosuppressieve medicatie tot 1 maand voor registratie.
    E.5 End points
    E.5.1Primary end point(s)
    Progression free survival (PFS; i.e. time from the first dose of iberdomide-cyclophosphamide-dexamethasone to progression or death from any cause, whichever comes first)
    Progressie vrije overleving
    E.5.1.1Timepoint(s) of evaluation of this end point
    every cycle
    Iedere cyclus
    E.5.2Secondary end point(s)
    ♦ Overall response rate. In this analysis we will consider the best response obtained during treatment according to the international myeloma working group (IMWG) criteria
    ♦ Safety and toxicity as defined by type, frequency and severity of adverse events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4
    ♦ Overall survival measured from first dose of iberdomide-cyclophosphamide-dexamethasone, to time of death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive.
    ♦ Time to response defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to the first objective documentation of PR or better.
    ♦ Duration of response defined as time from documentation of tumor response to disease progression.
    ♦ Time to second objective disease progression (PFS2) defined as time from first dose of iberdomide-cyclophosphamide-dexamethasone to 2nd disease progression or death from any cause.
    ♦ Time to next treatment (TTNT) defined as the date from first dose of iberdomide- cyclophosphamide-dexamethasone to first day when subject receives another myeloma treatment. Subjects who do not start new myeloma therapy are censored at the last known alive date or first dose date, whichever is later.
    - Overall response rate > effectiviteit van IberCD (volgens IMWG criteria)
    - Veiligheid en toxiciteit
    - Overall survival
    - Tijd tot respons
    - Respons duur
    - Tijd tot tweede objectieve ziekte
    - Tijd tot volgende behandeling
    E.5.2.1Timepoint(s) of evaluation of this end point
    every cycle
    iedere cyclus
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    laatste bezoek laatste deelnemer
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 25
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 35
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None / other study / standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-06-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-06-17
    P. End of Trial
    P.End of Trial StatusOngoing
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