NCT04891809

Isatuximab in Combination With Rd Compared to Rd in Elderly Patients (Aged ≥70 Years) With NDMM

Isatuximab in Combination With Lenalidomide-Dexamethasone Compared to Lenalidomide-Dexamethasone in Elderly Patients (Aged ≥70 Years) With Newly Diagnosed Myeloma: a Randomized Phase II Study (SGZ-2019-12650)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 198 (estimated)
• Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie · Academic / Other
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

Summary

As optimal tolerance is the key for developing new treatments for the very elderly population, the aim of the study is to compare the efficacy and tolerance of isatuximab in combination with lenalidomide+dexamethasone (Rd) versus Rd only in very elderly patients aged 70 years or older. ln sum, a clear and clinically highly relevant benefit is expected with the isatuximab-based triple combination compared to the standard Rd doublet.

Detailed description

The treatment goals in elderly patients with multiple myeloma (MM) are similar to those in younger patients: rapid and long-lasting symptom control, deep response and durable remissions as well as increased survival are at the forefront, similar to therapy goals in younger patients. Elderly patients frequently present with comorbidities, reduced treatment tolerance and greater frequency of treatment discontinuations. Hence, treatment needs to be adapted to the specific needs of this patient population. ln the recent decade lenalidomide-based therapies have been established as effective treatment modalities in elderly patients. In elderly patients lenalidomide + dexamethasone (Rd) is one of the most frequently used treatment regimens, which is effective and well tolerated. MM is a high unmet medical need and as a result, several agents are currently under clinical investigation in MM. Monoclonal antibodies (mAb) are one of the most promising groups of drugs in development in the treatment of MM with several of them demonstrating activity in this disease. lsatuximab is a highly effective monoclonal antibody with an excellent activity and tolerance profile, active as single agent therapy in patients with multiple prior lines of treatment. Presently several trials with isatuximab-lenalidomide containing treatment regimens are ongoing. The expected benefits of adding isatuximab to Rd over Rd alone in very elderly patients seem to outweigh possible risks by far. A greater depth of response is anticipated including greater number of MRD (minimal residual disease) negative patients, higher response rates, and longer progression free survival. Risk conferred with the addition of isatuximab are mainly restricted to a roughly 40% rate of infusion reactions, which usually are seen at the first infusion only. ln addition, there is an increased risk for grade 4 leukopenia, grade 2 and 3 thrombocytopenia, and grade 3 infection and fatigue.

Conditions

• Newly Diagnosed Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Isatuximab-Irfc 20 MG/ML [Sarclisa]	Induction: 10mg/kg on day 1,8,15,22 in cycle 1, subsequently on day 1, 15; every 28 days (q28 days) Maintenance: 10mg/kg, day1, q28 days until progression or intolerance but for a maximum of 24 cycles from start of maintenance
DRUG	Lenalidomide	Induction: 25mg\*, day 1-21, every 28 days (q28 days); Maintenance: 5-10mg, day 1-21, q28 days (according to individual tolerance) until progression or intolerance but for a maximum of 24 cycles from start of maintenance \*) for patients with moderate renal impairment (30≤ GFR (MDRD formula) \< 50 mL/min) starting dose is 10 mg
DRUG	Dexamethasone Oral	Induction: Patients aged \<75 years: 40mg, once weekly; Patients aged ≥75 years: 20mg, once weekly

Timeline

• Start date: 2021-10-20
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2021-05-18
• Last updated: 2025-04-10

Locations

14 sites across 3 countries: Austria, Greece, Serbia