Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

Multiple Myeloma Clinical Trial

Official title: Multicenter, Phase II, National and Open-label Study to Evaluate Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

Status Not yet recruiting

Clinical Trial Summary

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population.

Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

Clinical Trial Description

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population.

Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

Participants will be evaluated for study eligibility per protocol as defined in the Inclusion/Exclusion criteria . The screening period takes place 28 days prior to the baseline visit.

Frontline treatment: cohorts 1 and 2

Cohort 1: IBERDEX

• Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO).

• Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years:

20 mg), every 4 weeks, PO.

Cohort 2: IBERDARADEX

• Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, PO.

• Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years:

20 mg), every 4 weeks, PO.

• Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle

The study treatment in both cohorts will be until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first.

The trial has the following objectives:

Primary Objectives

PO1: To determine the efficacy of iberdomide in combination with dexamethasone (IBERDEX cohort 1) and also in combination with daratumumab and dexamethasone (IBERDARADEX cohort 2) in transplant ineligible NDMM patients, as measured by overall response rate (ORR) as well as the other response categories and especially the complete response rate (CRR) according to the International Myeloma Working Group (IMWG) response criteria 2016.

Secondary Objectives

SO1: To evaluate the efficacy in terms of minimal residual disease (MRD) with especial attention to the proportion of patients in MRD negative at 12 months of starting treatment as well as patients able to sustain it over time (according to the IMWG response criteria 2016).

SO2: To evaluate time to event data in the overall population and in the frail and non-frail population: Progression Free Survival (PFS) (from the time of inclusion in the trial until progression and/or death) and Overall Survival (OS).

SO3: To evaluate the changes in the immune profiling in order to better understand the outcomes in the overall population and in the non-frail and frail subgroups of patients.

SO4: To assess quality of life evolution through EQ-5D/5L, QLQ-C30 and MY20 questionnaires, at baseline and at months 4, 8, 12, 18, and 24.

SO5: To assess the safety of the combination of iberdomide + dexamethasone and iberdomide + dexamethasone + daratumumab. ;

Related Conditions & MeSH terms

• Multiple Myeloma

• NCT number: NCT05527340
• Study type: Interventional
• Source: PETHEMA Foundation
• Contact: Carmen López-Carrero
• Phone: (+34) 699 835 437
• Email: carmen@fundacionpethema.es
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2022
• Completion date: December 2029