This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital team work on a medical research study) study in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) and who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT). The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT
The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
294
Daratumumab SC 1800 mg * once every week for 8 weeks * then once every other week for 16 weeks * thereafter once every 4 weeks, until progression
Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression
Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Chru Jean Minjoz
Besançon, France
Ch Blois Simone Veil
Blois, France
Ch Fleyriat
Bourg-en-Bresse, France
Chru Brest Site Hopital Morvan
Brest, France
Chu de Caen Normandie
Caen, France
Hopital Prive Sevigne - Cesson
Cesson-Sévigné, France
Chu Dijon Bourgogne
Dijon, France
Chu de Grenoble
Grenoble, France
Gpe Hospitalier La Rochelle-Re-Aunis
La Rochelle, France
Ch Chartres Louis Pasteur-Le Coudray
Le Coudray, France
...and 13 more locations
Comparison of the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd): PFS
The primary objective is to compare the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) to that of Lenalidomide and Dexamethasone (Rd), in terms of PFS in frail subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant.
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Time-to-treatment failure
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Time-to-next treatment
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
PFS2 time
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Overall survival (OS) time
Overall survival (OS) time,
Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 84months
Complete remission (CR)
Percentage of participants with CR, as defined by the IMWG criteria, will be reported.
Time frame: From date of randomization until the date of first documented progression whichever came first, assessed up to 84months
Very good partial response (VGPR) or better.
VGPR or better, defined as VGPR or CR according to the IMWG criteria during or after the study treatment at the time of data cutoff.
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Overall response (CR + VGPR + partial response [PR]).
Overall response, defined as CR or VGPR or PR, according to the IMWG criteria
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Occurrence of grade 3 or more side effects.
Collecting all AE (grade 3 or more)
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Safety and tolerability of Daratumumab SC when administered in combination with Revlimid: NCI-CTCAE V5.0.
Evaluation of safety data by type, frequency, severity, relation to study drug, according to NCI-CTCAE V5.0.
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Evaluation of quality of life based on MY20 questionnaires
Treatment effects on patient reported outcomes and heath economic/resource utilization.
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Evaluation of quality of life based on EORTC C30 questionnaires
Treatment effects on patient reported outcomes and heath economic/resource utilization.
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Evaluation of quality of life based on EQ-5D questionnaires
Treatment effects on patient reported outcomes and heath economic/resource utilization.
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
Minimal residual disease (MRD) negative rate at 12 months.
Proportion of participants assessed as MRD negative
Time frame: after 12 months of treatment
Event Free Survival
Time frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
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