Clinical Trials /

Ixazomib -Daratumumab Without Dexamethasone (IDara) in Elderly Relapse Refractory Multiple Myeloma

NCT03757221

Description:

Multiple myeloma is an incurable hematological malignancy that affects older patients. Currently, despite recent progress, the disease relapses more or less quickly after initial treatment and requires the resumption of treatment with new drugs associated with cortisone, whose side effects are important. The investigators propose to conduct a phase 2 testing the combination ixazomib - daratumumab without dexamethasone.

Related Conditions:
  • Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib -Daratumumab Without Dexamethasone (IDara) in Elderly Relapse Refractory Multiple Myeloma
  • Official Title: A Multicentre Open-label Phase II Study of Ixazomib -Daratumumab Without Dexamethasone (IDara) in Elderly Relapse Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 18-070
  • NCT ID: NCT03757221

Conditions

  • Multiple Myeloma

Purpose

Multiple myeloma is an incurable hematological malignancy that affects older patients. Currently, despite recent progress, the disease relapses more or less quickly after initial treatment and requires the resumption of treatment with new drugs associated with cortisone, whose side effects are important. The investigators propose to conduct a phase 2 testing the combination ixazomib - daratumumab without dexamethasone.

Trial Arms

NameTypeDescriptionInterventions
Combination ixazomib + daratumumab without dexamethasoneExperimentalElderly Relapse Refractory Multiple Myeloma Patients treated by Combination ixazomib + daratumumab without dexamethasone

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Must be able to understand and voluntarily sign an informed consent form
    
              -  Must be able to adhere to the study visit schedule and other protocol requirements
    
              -  Age >= 65 years
    
              -  Subjects affiliated with an appropriate social security system.
    
              -  Life expectancy > 6 months
    
              -  Patients must have relapsed myeloma, and have been previously treated with Bortezomib,
                 Melphalan and Prednisone (VMP) or Lenalidomide and Dexamethasone (Rd), or both:
    
                   -  One or two line(s) of prior therapies
    
                   -  Patients must have Progressive Disease as defined by the IMWG as one of the
                      following (Kumar, 2016): Increase of 25% from lowest response value in any one or
                      more of the following:
    
                        -  Serum M-component (absolute increase must be ≥ 0.5 g/100 ml) and/or Urine
                           M-component (absolute increase must be ≥ 200 mg per 24 h) and/or
    
                        -  Only in patients without measurable serum and urine M-protein levels: the
                           difference between involved and uninvolved FLC levels (absolute increase
                           must be > 10 mg/l).
    
                        -  Bone marrow plasma cell percentage (absolute % must be ≥ 10%)
    
                        -  Definite development of new bone lesions or soft tissue plasmacytomas or
                           definite increase in the size of existing bone lesions or soft tissue
                           plasmacytomas
    
                        -  Development of hypercalcemia (corrected serum calcium > 11.5 mg/100 ml) that
                           can be attributed solely to the plasma cell proliferative disorder
    
                   -  Patients must have undergone prior treatment with VMP or Rd:
    
                        -  They must have received at least two cycles of therapy
    
                        -  Either at diagnosis or relapse
    
              -  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).
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
    
              -  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
    
              -  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 < 1.5 ULN
    
              -  Wash out period of at least 2 weeks from previous antitumor therapy or any
                 investigational treatment or 5 half-lives from previous antibodies.
    
              -  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.
    
            Criteria for women of childbearing potential:
    
            This protocol defines a female of childbearing potential as a sexually mature woman who:
    
              1. has not undergone a hysterectomy or bilateral oophorectomy or
    
              2. has not been naturally postmenopausal (amenorrhea following cancer therapy does not
                 rule out childbearing potential) for at least 24 consecutive months (ie, has had
                 menses at any time in the preceding 24 consecutive months)
    
                   -  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
    
                   -  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.
    
                   -  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.
    
                   -  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.
    
            Exclusion Criteria:
    
              -  Target disease exceptions: Solitary bone/solitary extramedullary plasmocytoma ;
                 Patients with non-secretory MM and non-measurable MM ; Evidence of central nervous
                 system (CNS) involvement
    
              -  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.
    
              -  Physical and laboratory test findings:
    
                   -  Patients on dialysis or with a Creatinine clearance < 30mL/min
    
                   -  SGOT or SGPT >3ULN
    
              -  Prohibited prior therapies
    
                   -  Prior local irradiation within two weeks before first dose
    
                   -  Previous anti-CD38 therapy.
    
                   -  Previous Ixazomib therapy
    
              -  Allergies and Adverse Drug Reaction:Known allergy to any of the study medications,
                 their analogues, or excipients in the various formulations of any agent.
    
              -  Refusal to consent or protected by a legal regime (guardianship, trusteeship)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:65 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Very Good Partial Response (VGPR) + Complete Response (CR) Rate using the IMWG response criteria
    Time Frame:12 months
    Safety Issue:
    Description: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 during the twelve months follow-up.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University Hospital, Caen

    Trial Keywords

    • Multiple Myeloma

    Last Updated

    July 5, 2019