Elderly Relapse Refractory Multiple Myeloma Patients MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Pharmaceutical Form:
Sponsors
CHU CAEN
Eligibility
Sex/Gender
All
Inclusion criteria
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/? ratio (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:
Exclusion criteria
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) 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary 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 ;Timepoint(s) of evaluation of this end point: 12 mois;Main Objective: determine the Very Good Partial Response (VGPR) + Complete response (CR) rate to Ixazomib plus Daratumumab in RR MM; Secondary Objective: · 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary 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 ;Timepoint(s) of evaluation of this end point: 3 et 6 mois | — |
Countries
France
Contacts
Public ContactPrincipal investigator
CHU CAEN
Outcome results
None listed