NDMM Patients Candidates for ASCT Comparing Extended VRD Plus vs. Isa-VRD vs. Isa-V-Iberdomide

ConditionNewly Diagnosed Multiple Myeloma

Trial statusRecruiting

Trial phasePhase 3

Trial typeInterventional

Biological sexAll

Age18-65

SponsorPETHEMA Foundation

About this trial

This is a Phase III open-label, 3-arm, parallel, randomized, controlled trial. The allocation ratio 1:1:1 and outcome assessment are blind to group allocation. Patients will be randomized from 3 arms. Patients will receive VRD extended + ASCT plus ERI or Isatuximab-VRD + ASCT or Isatuximab-VID + ASCT.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.

Patient must be able to understand the study procedures.

Patient has given voluntary written informed consent before performance of any studyrelated procedure non part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

Newly diagnosed multiple myeloma patient who requires start active treatment according to the 2014 IMWG criteria, namely clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcaemia, Anaemia, Renal Insufficiency, or Bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET-CT), and any one or more of the following biomarkers: clonal BMPC% ≥60%, i/u free light ratio ≥100 or > 1 focal lesions on MRI or PET/CT) [Lancet Oncol. 2014;15(12): e538-e548].

Disqualifiers

Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.

Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma.

Prior history of malignancies, other than multiple myeloma (except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or the breast), unless the patient has been free of the disease for ≥ 5 years.

Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and/or lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.

Trial design

Design model

Parallel

Treatments tested in this trial

Bortezomib
Drug
Bortezomib
Isatuximab
Drug
Isatuximab
Iberdomide
Drug
Iberdomide
Lenalidomide
Drug
Lenalidomide
Dexamethasone
Drug
Dexamethasone

Treatment groups

480 Participants

are divided into 3 treatment groups

Group A: Control arm (A)Active comparator 4 interventions

Group B: EXPERIMENTAL ARM (B): Extended VRD and Early Rescue InterventionExperimental treatment 5 interventions

Group C: EXPLORATORY ARM (C)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

Efficacy in terms of patients who are MRD-negative by NGF

Percentage of patients who are MRD-negative by next generation flow cytometry (NGF) after 18 cycles + ASCT comparing the efficacy of extended VRD + ASCT plus ERI \& (Arm B) vs. IsatuximabVRD + ASCT (Arm A).

Time frame

24 months

Secondary outcomes

Frequency of adverse events (AEs)

Number of patients who presented AEs in each arm to perform safety analysis. NOTE: Due to the experimental nature of the Arm C combination Isatuximab-Iberdomide-Bortezomib-Dex, a safety analysis will be performed with the first 5 patients included in each arm as per section, a second one when 25 patients in each arm have completed 3 cycles of therapy, and subsequent ones might be required if considered by the Primary-Investigator, Co-Primary-Investigator, Co-coordinators and Co-Investigator.

Time frame

Throughout the study. Approximately 78 months.

Progression-Free Survival (PFS)

Time from the start of treatment until the earliest date of documented disease progression or death due to any cause.

Time frame