multiple myeloma MedDRA version: 20.1 Level: LLT Classification code 10051381 Term: Myeloma recurrence System Organ Class: 100000004864
Conditions
Interventions
Trade Name: DARZALEX
Product Name: Daratumumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Concentration unit: mg/ml milligram(s)/millilitre
Con
Sponsors
Assistance Publique - Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1/ Adult patients (= 18 years old) 2/ Documented MM in relapse according to standard criteria and requiring initiation of a first line salvage therapy. 3/ Subject must have received one prior line of therapy for MM. 4/ Subject must have achieved a response (PR or better) to the prior regimen. 5/ Subject must have an ECOG Performance Status score of 0, 1, or 2. 6/ For subjects experiencing serious toxicities resulting from previous therapy (including peripheral neuropathy), the toxicities must have been resolved or stabilized. 7/ Signed informed consent 8/ Affiliation to a social security system or equivalent (recipient or assign) 9/ Effective method of contraception for the duration of treatment and 3 months after the last dose for women and men with a partner of childbearing age: • Progestin-only pill associated with inhibition of ovulation • Hormonal methods of contraception, including oral contraceptive pills containing a combination of estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) • non-hormonal IUD • Bilateral tubal occlusion • Vasectomized partner with documented azoospermia 90 days after procedure and who received a medical assessment of surgical success • Intrauterine hormone release system (IUS) • Complete Abstinence: Complete abstinence is defined as the complete avoidance of heterosexual intercourse. Complete abstinence is an acceptable form of contraception for all study drugs and must be used throughout the duration of the study and for the duration of time as specified above. It is not necessary to use any other method of contraception when complete abstinence is elected. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 284
Exclusion criteria
Exclusion criteria: 1/ Evidence of refractoriness or intolerance to lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody). If previously treated with a lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody) -containing regimen, the subject is excluded if he or she: • Discontinued due to any severe adverse event related to prior lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody) treatment, or • If, at any time point, the subject was refractory to any dose of lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody). Refractoriness to lenalidomide and/or daratumumab is defined either as: o Subjects whose disease progressed within 60 days of lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody) administration; or o Subjects whose disease is nonresponsive while on lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody). Nonresponsive disease is defined as either failure to achieve at least a minimal response or development of progressive disease while on lenalidomide and/or daratumumab (or another anti CD38 monoclonal antibody). 2/ Subject has received an allogenic stem cell transplant (regardless of timing). 3/ Subjects planning to undergo a stem cell transplant prior to progression of disease on this study, ie, these subjects should not be enrolled in order to reduce disease burden prior to transplant. 4/ Subject has a history of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence within 3 years). 5/ Subject has known MM meningeal involvement. 6/ Subject has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis. 7/ Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that, in the opinion, of the investigator would constitute a hazard for participating in this study. 8/ Subject has known uncontrolled chronic obstructive pulmonary disease (COPD) 9/ Subject has clinically significant cardiac disease. 10/ Subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. 11/ Creatinine clearance =30 mL/min (MDRD method) (lenalidomide dose adjustment will be considered for subjects with creatinine clearance 30-60 mL/min). 12/ Hypersensitivity to the active substance or to any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The present randomized trial is primarily designed to show the non-inferiority in overall survival at 4 years of the Dara-Len-Dex combination for treatment of MM at first relapse administered for a fixed duration of 24 months (experimental arm) versus continuous administration (control arm) until disease progression;Secondary Objective: Secondary objectives are: • To compare: - the response rate after salvage therapy and achievement of a minimal residual disease - the overall response rate following salvage therapy - progression-free survival (PFS) - Serious adverse events • To compare the impact of the treatment strategies on Quality of Life (QoL). • To perform a cost-effectiveness analysis • To perform a budget impact analysis ;Primary end point(s): Overall survival (OS) at 4 years after randomization and initiation of salvage therapy;Timepoint(s) of evaluation of this end point: 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Response rate according to the IMWG criteria (Durie BG, et al. Leukemia. 2006;20:1467–1473; Rajkumar SV, et al. Blood. 2011;4691-4695), during or after the study treatment at the time of data cutoff. • Overall response rate, defined as the proportion of subjects who achieve CR or PR according to the IMWG criteria, following salvage therapy. • PFS which is defined as the duration from the date of randomization to either progressive disease, according to the IMWG criteria or death, at 4 years after randomization. • Incidence of adverse events within the 4 years after randomization. • QoL will be evaluated after randomization every 12 weeks until disease progression and then at last follow-up based on the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) and the EQ-5D 5L (EuroQol - five dimension - five levels). • The Incremental cost-effectiveness ratios (ICERs) expressed in cost per quality adjusted life year (QALY) gained, in cost per Life Year Gained, and in cost per progression free year gained. • The budget impact analysis based upon target and prevalent populations’ estimations.;Timepoint(s) of evaluation of this end point: 4 years | — |
Countries
France
Contacts
Public ContactDRCI Hôpîtal Saint-Louis
Assistance Publique - Hôpitaux de Paris (AP-HP)
Outcome results
None listed