Schéma : This is a multicenter, Phase 3, randomized, open-label study comparing daratumumab, pomalidomide and low-dose dexamethasone (DaraPomDex) with pomalidomide and low-dose dexamethasone (PomDex) in subjects with relapsed or refractory Multiple Myeloma who have received at least 1 prior treatment regimen with both lenalidomide and a proteasome inhibitor and have demonstrated disease progression. Subjects will be randomized in a 1:1 ratio to receive either DaraPomDex or PomDex. The original design of this study was to treat subjects with daratumumab for intravenous (IV) infusion (Dara IV); however, as of Amendment 1, all new subjects will be dosed subcutaneously with daratumumab co-formulated with recombinant human hyaluronidase rHuPH20 (hereafter referred to as Dara SC). Subjects who already began treatment with Dara IV (ie, prior to Amendment 1) will have the option to switch to Dara SC on Day 1 of any cycle starting with Cycle 3 or later for the remainder of their participation in the study, and they will be counted toward the total of 302 subjects. Subjects will receive treatment until disease progression or unacceptable toxicity. Drug administration and follow-up visits will occur more frequently for early cycles (e.g., weekly or bi-weekly). Disease evaluations will occur every cycle and consist mainly of measurements of myeloma proteins. Subject safety will be assessed throughout the study. The primary endpoint will be progression-free survival (PFS). Study end is anticipated at approximately 5 years after the last subject is randomized.
Study arms:
- Experimental: Daratumumab+Pomalidomide+Dexamethasone
Daratumumab at a dose of 16 mg/kg administered as an IV infusion (Dara IV) or 1800 mg subcutaneously (Dara SC) at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Pomalidomide 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle Dexamethasone 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle
Interventions:
Drug: Daratumumab
Drug: Pomalidomide
Drug: Dexamethasone
- Active Comparator: Pomalidomide + Dexamethasone
Pomalidomide 4 mg orally (PO) on Days 1 through 21 of each 28-day cycle Dexamethasone 40 mg (20 mg for patients ≥75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle
Interventions:
Drug: Pomalidomide
Drug: Dexamethasone
Current primary outcome:
Comparison of Progression Free Survival between treatment arms [ Time Frame: Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 3 years)] ]
Current secondary outcomes:
- Overall response rate [ Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)] ]
- Very Good Partial Response (VGPR) or better rate [ Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)] ]
- Complete Response or better rate [ Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years)] ]
- Minimal Residual Disease negativity rate [ Time Frame: Frame: From Randomization until PD (approximately up to 3 years). Assessed at suspected CR and, 6, 12, 18, 24 months post CR/sCR and every 12 months thereafter in subjects with CR until PD ]
- Time to response [ Time Frame: Assessed monthly from randomization up to first documented CR or PR (approximately up to 3 years) ]
- Duration of response [ Time Frame: Assessed monthly from Randomization until PD, (approximately up to 3 years) ]
- Time to next therapy [ Time Frame: From randomization until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 3 years) ]
- Overall survival [ Time Frame: From randomization until death from any cause (up to 5 years) ]
- Safety (adverse events) [ Time Frame: Continuously throughout the study, starting from informed consent until 30 days after last study treatment (approximately up to 3 years) ]
- Scale and domain scores of the EORTC QLQ-C30 and EORTC QLQ-MY20 [ Time Frame: Day 1 of each treatment cycle, at end of treatment, and every 4 weeks post treatment until PD (approximately up to 3 years) ]
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Item is a cancer-specific PRO measure. It includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma Module is a MM PRO measure to be used in conjunction with the EORTC QLQ-C30 for assessing HRQoL in patients with MM. It includes 20 items resulting in 2 symptom scales (disease symptoms and side-effects of treatment), 1 function scale (future perspective), and a single item on body image.
- EQ-5D-5L health utility values [ Time Frame: Day 1 of each treatment cycle, at end of treatment, and every 4 weeks post treatment until PD (approximately up to 3 years) ]
The EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today"
- Immunomodulatory effects of daratumumab on T cells [ Time Frame: Day 1 of cycles 1 , 3, 6, 12 predose and at suspected CR and at PD (approximately up to 3 years) ]
- Daratumumab pharmacokinetic concentrations (Daratumumab IV and Dararatumumab SC) [ Time Frame: IV: Day 1 of cycles 1,3,7 predose and at the end of Infusion and at 4 and 8 weeks after the last dose. SC: Days 1,4 of cycles 1,3, Day 1 of cycles 5,7,12 and at 4 and 8 weeks after the last dose ]
- Daratumumab immunogenicity, rHuPH20 immunogenicity in subjects who receive Daratumumab SC [ Time Frame: IV: Day 1 of first cycle predose, Day 1 of cycle 7 predose and at 4 and 8 weeks after the last dose (approx up to 3 years), SC and rHuPH20: Day 1 of cycle 1, 5, 7, 12 predose and at 4 and 8 weeks after the last dose ]
Phase : III
Stade : NA
Rechute, Réfractaire