NCT04096066

A Trial That Compare Two Treatments in Newly Diagnosed Myeloma Patients Not Eligible for Transplant

Carfilzomib - Lenalidmide - Dexamethasone (KRd) Versus Lenalidomi - Dexamethasone (Rd) in Newly Diagnosed Myeloma Patients Not Eligible for Autologous Stem Cell Transplantation: a Randomized Phas III Trial

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 84 (actual)
• Sponsor: Fondazione EMN Italy Onlus · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

The combination of lenalidomide plus low-dose dexamethasone (Rd) is considered the new standard for elderly newly diagnosed multiple myeloma (NDMM) patients. The combination carfilzomib plus lenalidomide-dexamethasone (KRd) in relapsed-refractory MM patients improved the progression-free survival (PFS) of approximately 1 year compared to standard Rd treatment. In a small phase 2 trial (23 pts) the KRd combination in elderly NDMM pts showed a complete response (CR) rate of 79% and a PFS at 3 years of 80%. Cardiovascular adverse events are the most limiting toxicities, especially in elderly patients.

Detailed description

This protocol is a randomized, multicenter study designed to determine the MRD negativity and the PFS of KRd treatment regimen. Patients will be randomized in a 1:1 ratio to receive carfilzomib-lenalidomide-dexamethasone (KRd - Arm A) or lenalidomide-dexamethasone (Rd - Arm B). Patients will be stratified basing on international staging system (ISS) and fitness status using a web-based procedure completely concealed to study participants. All consecutive patients ≥ 65 years with newly diagnosed MM will be enrolled in a large randomized study during a period of 24 months. Patients will be treated until disease progression or intolerance to the therapy. The only exception is for patients enrolled in KRd arm who achieve at least a VGPR during the first year of treatment and in sustained MRD negativity (MRD negative at least at 10-5 after one and two years of therapy): these patients will stop carfilzomib administration after 2 years, whereas treatment with lenalidomide and dexamethasone will be continued.

Conditions

• Multiple Myeloma
• New Diagnosis Tumor

Interventions

Type	Name	Description
DRUG	Carfilzomib	* 20 mg/m2 IV on day 1 of cycle 1 enhanced to 56 mg/m2 on days 8, and 15 of cycle 1; * 56 mg/m2 IV on days 1, 8 and 15 in cycles 2-12; * 56 mg/m2 IV on days 1 and 15 from cycle 13 and onwards.
DRUG	Lenalidomide	\- 25 mg orally on days 1-21 of each cycle.
DRUG	Dexamethasone	\- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is to be repeated every 28 days. Patients that achieve at least a VGPR within the first year of study treatment and in sustained MRD negativity (MRD negative at least at 10-5 after 1 and 2 years of therapy) will stop carfilzomib administration after 2 years and will continue with lenalidomide and dexamethasone treatment until disease progression or intolerance to the therapy. Other patients will continue carfilzomib administration until disease progression or intolerance. For patients \>75 years of age, the dose of dexamethasone is 20 mg/day on Days 1, 8, 15 and 22 of each treatment cycle.

Timeline

• Start date: 2019-07-01
• Primary completion: 2026-01-01
• Completion: 2026-01-01
• First posted: 2019-09-19
• Last updated: 2025-01-15

Locations

40 sites across 1 country: Italy