Multiple Myeloma in Relapse, Multiple Myeloma, Refractory
Conditions
Brief summary
Study a quadruplet-based regimen with Minimal Residual Disease (MRD) 10-5 negative rate as primary end point in patients with early Relapsed or Refractory Multiple Myeloma. Therapeutic study, phase II, prospective, multicenter, open-label. The patients will be treated until progression. Each cycle of treatment lasts 28 days. Cycle 1 to 13 : treatment phase After cycle 13 : maintenance phase
Interventions
DRUGIsatuximab
Isatuximab by IV route - Cycle 1 : 10mg/kg on days 1, 8, 15 and 22 per 28 days cycle. After cycle 1 : 10mg/kg on days 1 and 15 per 28 days cycle
DRUGCarfilzomib
Carfilzomib by IV route - Cycle 1 : 20/27 mg/m² on days 1-2, 8-9, 15-16 per 28 days cycle. Cycle 2-13 : 56mg/m² on days 1, 8, 15 per 28 days cycle. After cycle 13 : 56mg/m² on days 1 and 15 per 28 days cycle.
DRUGPomalidomide
Pomalidomide by oral route - Cycle 1-2 : 3mg on days 1 to 21 per 28 days cycle. After cycle 2 : 4mg on days 1 to 21 per 28 days cycle.
DRUGDexamethasone
Dexamethasone by oral route - Cycle 1-13 : 40/20 mg on days 1, 8, 15 and 22. Cycle 2-13 : 56mg/m² on days 1, 8, 15 per 28 days cycle. After cycle 13 : 56mg/m² on days 1 and 15 per 28 days cycle.
Sponsors
Sanofi
Celgene
Amgen
Intergroupe Francophone du Myelome
Poitiers University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. Male or female, age 18 years or older 4. Life expectancy of \> 6 months. 5. Must have a in R1 and R2 relapse Multiple Myeloma with a measurable disease : * 1 to maximum 2 lines of therapy prior to study entry * Relapse Refractory or primary refractory or relapse * Must have received prior treatment with a Lenalidomide-containing regimen for at least 2 consecutive cycles 6. Must have measurable disease as defined by the following: must have a clearly detectable and quantifiable monoclonal M-component value in the serum and/or urine : * IgG/IgA (serum M-component \> 5g/l), * Light chain (serum M-component \>1g/l or Bence Jones \> 200mg/24H), * Serum FLC assay (including for IgD isotypes): involved FLC level \> 10 mg/dl provided serum. FLC ratio is abnormal for patients not measurable on any of the 3 above criteria. 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 8. Wash out period without MM treatment must be of 28 days minimum before C1D1, except for anti CD-38 (See
Exclusion criteria
#10). 9. Adequate bone marrow function, documented within 72 hours and without transfusion 72 hours prior to the first intake of investigational product (C1J1) with no growth factor support (one week), defined as : * Absolute neutrophils ≥ 1 x109/L, * Untransfused Platelet count ≥ 75 x109/L, * Hemoglobin ≥ 8.5 g/dL. 10. Adequate organ function defined as : * Serum total bilirubin \< 2x upper limit of normal (ULN), * Clearance creatinine ≥ 30ml/min, * Serum SGOT/AST or SGPT/ALT \< 3x upper limit of normal (ULN). 11. Patients affiliated to an appropriate social security system. 12. A man who is sexually active with a pregnant female or a FCBP\* must agree to use a barrier method of birth control eg, condom with spermicidal foam/gel/film/cream/suppository, even if he has had a vasectomy. All men must also not donate sperm, spermatozoa during the study, for 5 months following treatment discontinuation. 13. A woman FCBP\* must understand and agree to use 2 reliable effective methods (a very effective method and an effective additional method) of contraception simultaneously without interruption : * For at least 28 days before starting experimental treatments, * Throughout the entire duration of experimental treatments, * During dose interruptions, * And for at least 5 months after the last dose of experimental treatments. 14. All patients must agree to not donate blood during the treatment period, interruptions of treatment and at least 5 months after the last dose of treatment. 15. All patients must understand and accept to comply with the conditions of the Pomalidomide pregnancy prevention plan (Appendix of the protocol).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of trial treatment | Up to 5 years | Fraction of patients who experience a Minimal Residual Disease (MRD) 10-5 per IMWG (International Myeloma Working Group) criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of trial treatment | Up to 5 years | List of AE frequency (AE assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 5.0) |
| Depth of response to the trial treatment | Up to 5 years | Per International Myeloma Working Group (IMWG) criteria |
| Progression Free survival | Up to 5 years | Time to relapse or death, whichever occurs first |
Countries
France
Outcome results
None listed