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    Summary
    EudraCT Number:2018-001646-34
    Sponsor's Protocol Code Number:18-070
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-05-16
    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 ConcernedFrance - ANSM
    A.2EudraCT number2018-001646-34
    A.3Full title of the trial
    A MULTICENTRE OPEN-LABEL PHASE II STUDY OF IXAZOMIB -DARATUMUMAB WITHOUT DEXAMETHASONE (IDARA) IN ELDERLY RELAPSE REFRACTORY MULTIPLE MYELOMA.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A MULTICENTRE OPEN-LABEL PHASE II STUDY OF IXAZOMIB -DARATUMUMAB WITHOUT DEXAMETHASONE (IDARA) IN ELDERLY RELAPSE REFRACTORY MULTIPLE MYELOMA.
    A.4.1Sponsor's protocol code number18-070
    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 SponsorCHU CAEN
    B.1.3.4CountryFrance
    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 supportPHARMACEUTICAL INDUSTRY
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCHU CAEN
    B.5.2Functional name of contact pointPrincipal investigator
    B.5.3 Address:
    B.5.3.1Street AddressIHBN, CHU CAEN
    B.5.3.2Town/ cityCAEN
    B.5.3.3Post code14033
    B.5.3.4CountryFrance
    B.5.4Telephone number33231272122
    D. IMP Identification
    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
    Elderly Relapse Refractory Multiple Myeloma Patients
    E.1.1.1Medical condition in easily understood language
    Elderly Relapse Refractory Multiple Myeloma Patients
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    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
    determine the Very Good Partial Response (VGPR) + Complete response (CR) rate to Ixazomib plus Daratumumab in RR MM
    E.2.2Secondary objectives of the trial
    · To determine Safety of Ixazomib plus Daratumumab (type, frequency, severity, and relationship of adverse events to study treatment). Incidence of Treatment Emergent Adverse Event , Serious Adverse Event and laboratory abnormalities using National Cancer Institute common toxicity criteria
    · To determine the clinical benefit rate (CBR, Minor response or better). MR will be determined using the criteria of the European Organisation for Blood and Marrow Transplantation criteria
    · To determine ORR including Partial Response (PR), Very Good Partial Response , Complete Response and minor response (MR) to Daratumumab plus Ixazomib at 3 months and 6 months of treatment
    · To determine progression-free survival
    · To determine time to progression
    · To determine time to response
    · To determine the Duration of Response
    · To determine Overall Survival
    · To determine difference in response rates and survival according to prior exposure to VMP versus RD
    · To assess Quality of Life
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Must be able to understand and voluntarily sign an informed consent form
    2. Must be able to adhere to the study visit schedule and other protocol requirements
    3. Age >= 65 years
    4. Subjects affiliated with an appropriate social security system.
    5. Life expectancy > 6 months
    6. Patients must have relapsed myeloma, and have been previously treated with Bortezomib, Melphalan and Prednisone (VMP) or Lenalidomide and Dexamethasone (Rd), or both:
    7. Patients must have a clearly detectable and quantifiable monoclonal M-component value:
    IgG (serum M-component > 10g/l)
    IgA (serum M-component > 5g/l)
    IgD (serum M-component > 0.5g/l)
    Light chain (serum M-component >1g/l or Bence Jones > 200 mg/24H)
    In patients without measurable serum and urine M-protein levels when the absolute serum Free Light chain (sFLC) is ≥100 mg/l and an abnormal sFLC K/λ ratio (<0.26 and >1.65) is found (Dispenzieri, 2008).
    8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
    9. Adequate bone marrow function within 5 days prior to 1st drug intake (cycle1, day 1, C1D1), without transfusion nor growth factor support within 5 days prior to 1st drug intake, defined as:
    Absolute neutrophils ≥ 1000/mm3
    Platelets ≥ 50000/mm3
    Haemoglobin ≥ 8.5g/dl
    10. Adequate organ function defined as:
    Serum creatinine clearance (MDRD formula) ≥30 ml/min
    Serum SGOT or SGPT < 3.0 X upper limit of normal (ULN)
    Serum total bilirubin < 2.0 mg/dL
    11. Wash out period of at least 2 weeks from previous antitumor therapy or any investigational treatment or 5 half-lives from previous antibodies.
    12. Women who are partners of men and of childbearing potential must be practicing one of the following methods of birth control: subcutaneous hormonal implant, levonorgestrel releasing intra-uterine system, medroxyprogesterone acetate depot, tubal sterilization, ovulation inhibitory progesterone only pills, or sexual intercourse with a vasectomized male partner (vasectomy must be confirmed by 2 negative semen analyses). Or women will commit to absolute and continuous abstinence confirmed to her physician on a monthly basis. Childbearing potential*. Contraception will start during therapy including dose interruptions, for 4 months after discontinuation of Ixazomib and Daratumumab.
    13. A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 28 days prior to dosing and the second within 48 hours prior to dosing, and remain on a highly effective method of birth control. The two methods of reliable contraception must include one highly effective method and one additional effective (barrier) method. FCBP must be referred to a qualified provider of contraceptive methods if needed. The following are examples of highly effective and additional effective methods of contraception:
    · Highly effective methods:
    Intrauterine device (IUD)
    Hormonal (birth control pills, injections, implants)
    Tubal ligation
    Partner’s vasectomy
    · Additional effective methods:
    Male condom
    Diaphragm
    CervicalCap
    14. Serum (urine in the case where serum is not possible in a timely manner) pregnancy test to be performed for all women of childbearing potential regularly during the study, In addition, a pregnancy test may be done at any time during the study at the discretion of the investigator if a subject misses a period or has unusual menstrual bleeding.
    15. A woman of childbearing potential must remain on a highly effective method of birth control. Contraception must begin 4 weeks before initiating treatment with Ixazomib and Daratumumab, during therapy, during dose interruptions and continuing for 4 months following discontinuation of Ixazomib and Daratumumab. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.
    16. A man who has not had a vasectomy and who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control eg, condom with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study, for 4 months following discontinuation of Ixazomib and Daratumumab. The exception to this restriction is that if the subject’s female partner is surgically sterile, a second method of birth control is not required.
    E.4Principal exclusion criteria
    1. Target disease exceptions:
    · Solitary bone/solitary extramedullary plasmocytoma
    · Patients with non-secretory MM and non-measurable MM
    · Evidence of central nervous system (CNS) involvement
    2. Medical history and Concurrent disease:
    · Subjects with prior (≤ 5 years) or concurrent invasive malignancies except the following:
    Adequately treated basal cell or squamous cell skin cancer
    Incidental finding of low grade (Gleason 3+3 or less) prostate cancer
    Any cancer from which the subject has been disease free for at least 3 years.
    · Subject with known/underlying medical conditions that, in the investigator’s opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes or uncontrolled coronary artery disease)
    · Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including:
    NYHA functional classification III or IV congestive heart failure LVEF (Left Ventricular Ejection Fraction) ≥45%
    Uncontrolled angina, hypertension or arrhythmia Myocardial infarction in the past 6 months
    · Subjects with grade 2 or greater peripheral neuropathy (as per NCI-CTCAEv4.0)
    · Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen.
    · Known positive for HIV or active hepatitis B or C.
    · Subjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
    · Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
    · Subjects with a history of moderate or severe persistent asthma within the past 2 years (see appendix), or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
    · Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of Ixazomib including difficulty swallowing.
    3. Physical and laboratory test findings:
    · Patients on dialysis or with a Creatinine clearance < 30mL/min
    · SGOT or SGPT >3ULN
    4. Prohibited prior therapies
    · Prior local irradiation within two weeks before first dose
    · Previous anti-CD38 therapy.
    · Previous Ixazomib therapy
    5. Allergies and Adverse Drug Reaction:
    Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
    6. Refusal to consent or protected by a legal regime (guardianship, trusteeship)
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the Very Good Partial Response (VGPR) + Complete Response (CR) Rate using the IMWG response criteria. Using IMWG criteria for best response reached at any time
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 mois
    E.5.2Secondary end point(s)
    · Assess safety by type, frequency, severity, relationship of adverse events to study treatment and changes in vital signs, physical exams. Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and laboratory abnormalities using National Cancer Institute (NCI) common toxicity criteria (CCTAE V4).
    · Determine the Clinical Benefit Rate (CBR = sCR + CR + PR + MR), and duration of Clinical Benefit using EBMT criteria at 3 months and six months.
    · Determine the OS (from the date of inclusion to last date of follow-up) of patients treated with Ixazomib + Daratumumab, Progression-free Survival (PFS), Event-free Survival (EFS) and time to progression (TTP).
    · Secondary efficacy variables for study treatment include:
    o Time to progression (TTP) obtained with study treatment versus the patient’s TTP(s) on prior therapies for MM
    o Duration of Response (DOR)
    · Assess QoL using EORTC QLQ30, MY20 and EQ5D-3L
    · Compare PFS, ORR, DOR, DCR, and OS obtained with Ixazomib plus Daratumumab and in patients with International Staging System (ISS) Stages II/III versus ISS Stage I at diagnosis
    E.5.2.1Timepoint(s) of evaluation of this end point
    3 et 6 mois
    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 No
    E.6.4Safety No
    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 concerned30
    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 No
    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
    Last Visit of the Last Subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    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) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 70
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state70
    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)
    traitement jusqu'à progression
    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 Decision2018-07-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-01-11
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2024-12-19
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