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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO)
Dexamethasone 40 mg (PO) (or 20 mg (PO) if patient ≥ 75 years old) should be administered on the days 1, 8, 15 and 22 of every 4-week cycle.
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 Cycles will be of 4 weeks of duration (28 days).
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Son Llatzer
Palma de Mallorca, Spain
Clínica Universidad de Navarra
Pamplona, Spain
Hospital Universitario de Salamanca
Salamanca, Spain
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Hospital Universitario Virgen del Rocío
Seville, Spain
Hospital Universitario y Politécnico La Fe de Valencia
Valencia, Spain
Overall Response Rate (ORR)
The percentage of participants with a confirmed partial response (PR) or better (PR, Very good partial response (VGPR), Complete response (CR), stringent complete response (sCR)).Response rates will be monitored monthly, but the study will report the % of patients achieving CR rate at month 12, 18, 24 and yearly thereafter.
Time frame: Throught the study period. Approximately 6 years.
Complete Response Rate (CRR)
The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR).
Time frame: Throught the study period. Approximately 6 years.
Minimal Residual Disease (MRD) negativity rate
The percentage of participants who are MRD negative by next-generation flow cytometry (NGF), PET/CT, and mass spectrometry.
Time frame: Throught the study period. Approximately 6 years.
Progression-Free Survival (PFS)
Time from the date of randomization until the earliest date of documented disease progression or death due to any cause.
Time frame: Throught the study period. Approximately 6 years.
Overall Survival (OS)
Time from the date of randomization until the date of death due to any cause
Time frame: Throught the study period. Approximately 6 years.
Changes in the immune profiling.
Relative distribution and immunophenotype of inmune profiling from baseline onto treatment, remission and disease progression.
Time frame: Throught the study period. Approximately 6 years.
Health status/quality of life
Global health status/quality of life based on patient reported outcome: EQ-5D/5L questionnaire.
Time frame: Baseline and throught the first 24 months.
Health status/quality of life
Global health status/quality of life based on patient reported outcome: QLQ-C30 questionnaire.
Time frame: Baseline and throught the first 24 months.
Health status/quality of life
Global health status/quality of life based on patient reported outcome: MY20 questionnaire.
Time frame: Baseline and throught the first 24 months.
Frequency and percentage of deaths and primary cause of death.
Incidence of deaths and primary cause of death for safety analysis.
Time frame: Throught the study period. Approximately 6 years.
Incidence of adverse events (AEs).
Incidence of adverse events (AEs).
Time frame: Throught the treatment period. Approximately 4 years.
Percentage of patients discontinuing therapy due to AEs.
Percentage of patients discontinuing therapy due to AEs.
Time frame: Throught the treatment period. Approximately 4 years.
Percentage of patients requiring dose modifications.
Percentage of patients requiring dose modifications.
Time frame: Throught the treatment period. Approximately 4 years.
Percentage of patients with changes in laboratory analytes from the hematology and blood chemistry panel.
Percentage of patients with changes in laboratory analytes from the hematology and blood chemistry panel.
Time frame: Throught the treatment period. Approximately 4 years.
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