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

NCT05558319 | Not Yet Recruiting Phase 3

• 1 other identifier: GEM21menos65
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 68

Brief Summary

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.

Conditions

Newly Diagnosed Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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).

  24 months

Secondary Outcomes (2)

• Frequency of adverse events (AEs)

  Throughout the study. Approximately 78 months.

• Progression-Free Survival (PFS)

  Throughout the study. Approximately 78 months

Other Outcomes (5)

• Overall Response Rate (ORR)

  Throughout the study. Approximately 78 months

• Complete Response Rate (CRR)

  Throughout the study. Approximately 78 months

• Time to Response (TTR)

  Throughout the study. Approximately 78 months

Study Arms (3)

Control arm (A)

ACTIVE COMPARATOR

INDUCTION: Isatuximab + VRD, 4 cycles. Isatuximab (IV) 10 mg/Kg, 1st cycle D: 1,8,15, 22. Cycles 2-4: D 1,15. Bortezomib (SC) 1.3 mg/m2, D:1, 4, 8, 11. Lenalidomide (PO) 25mg, D:1-21. Dexamethasone (PO) 40 mg, D: 1-4, 9-12. ASCT. The conditioning regimen is melphalan 200 mg/m2. CONSOLIDATION: Isatuximab + VRD, 2 cycles. Isatuximab (IV) 10 mg/Kg. D 1-15. Bortezomib (SC) 1.3 mg/m2, D:1, 4, 8, 11. Lenalidomide (PO) 25mg, D:1-21. Dexamethasone (PO) 40 mg, D: 1-4, 9-12. CONTINUOUS TREATMENT: Lenalidomide and monthly Isatuximab until progression, unacceptable toxicity, patient withdrawal, loss to follow up or death. During continuous treatment, dexamethasone 40 mg is used as a standardized premedication for Isatuximab.

Drug: Bortezomib; Drug: Isatuximab; Drug: Lenalidomide; Drug: Dexamethasone

EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention

EXPERIMENTAL

INDUCTION: Includes two experimental lines: 1. VRD extended to 18 cycles: Induction (VRDx6): Bortezomib (SC) 1.3 mg/m2, D: 1, 4, 8, and 11 (Q4W). Lenalidomide 25 mg (PO), D: 1-21 (Q4W). Dexamethasone 40 mg (PO) D 1 to 4 and 9 to 12 (Q4W). Isatuximab (IV) 10 mg/kg, D: 1, 8, 15, and 22 (Q4W) and D: 1-15 in subsequent cycles. 2. Early detection of treatment failure and Early Rescue Intervention (ERI): Isatuximab-Iberdomide-Dexamethasone in continuous treatment. Isatuximab (IV) 10mg/kg Cycle 1: Days 1, 8, 15, and 22 (Q4W). Cycles 2 onwards: Days 1 and 15 (Q4W). Isatuximab will be infused monthly after 1 year treatment (Day 1 Q4W) including ASCT. Iberdomide (PO) 1,6 mg. D: 1-21 (Q4W). Dexamethasone (PO) 40 mg. D: 1, 8, 15, and 22 (Q4W). ASCT. The conditioning regimen is melphalan 200 mg/m2. CONSOLIDATION (VRDx2)- Extended VRD: VDx10, followed by lenalidomide plus dexamethasone maintenance. CONTINUOUS TREATMENT: Lenalidomide 15 mg, D: 1-21, and dexamethasone 20 mg, D: 1-4 (Q4W).

Drug: Bortezomib; Drug: Isatuximab; Drug: Iberdomide; Drug: Lenalidomide; Drug: Dexamethasone

EXPLORATORY ARM (C)

EXPERIMENTAL

INDUCTION: Iberdomide plus Isatuximab, bortezomib and dexamethasone (four cycles). Isatuximab (IV) 10 mg/kg D 1, 8, 15, and 22 in the first Q4W; and days 1-15 in subsequent cycles. Iberdomide (PO) at 1.6 mg on days 1-21 of every 4-week cycle. Bortezomib (SC) at 1.3 mg/m2 on days 1, 4, 8, and 11 of every 4-week cycle. Dexamethasone 40 mg (PO) D 1-4, 9-12 (Q4W). ASCT. The conditioning regimen is melphalan 200 mg/m2. CONSOLIDATION: two cycles (Q4W) of Isatuximab, Iberdomide, Bortezomib and Dexamethasone, as in induction, starting approximately 2 months after hospital discharge or 3 months after transplantation. Isatuximab will be infused monthly since the start of continuous therapy (after the second cycle of consolidation). CONTINUOUS TREATMENT: Iberdomide and monthly Isatuximab until progression, unacceptable toxicity, patient withdrawal, loss to follow up or death. During continuous treatment, dexamethasone 40 mg is used as a standardized premedication for Isatuximab.

Drug: Bortezomib; Drug: Isatuximab; Drug: Iberdomide; Drug: Dexamethasone

Interventions

Bortezomib DRUG

Bortezomib

Control arm (A); EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention; EXPLORATORY ARM (C)

Isatuximab DRUG

Isatuximab

Control arm (A); EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention; EXPLORATORY ARM (C)

Iberdomide DRUG

Iberdomide

EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention; EXPLORATORY ARM (C)

Lenalidomide DRUG

Lenalidomide

Control arm (A); EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention

Dexamethasone DRUG

Dexamethasone

Control arm (A); EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention; EXPLORATORY ARM (C)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \[Lancet Oncol. 2014;15(12): e538-e548\].
• Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Patient must be ≤ 65 years of age.
• Patient must have adequate organ function, defined as follows:
• Absolute neutrophil count (ANC) ≥1.0 X 109/L without G-CSF use in the prior 7 days
• Hemoglobin ≥8.0 g/dL (prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted)
• Platelets ≥ 75 x 109/L in participants in whom \<50% of bone marrow nucleated cells are plasma cells and ≥ 50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test).
• Calcium Corrected serum calcium ≤13.5 mg/dL (≤3.4 mmol/L); or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L).
• Total bilirubin ≤2 X ULN
• ALT ≤2.5 X ULN
• AST ≤2.5 X ULN

You may not qualify if:

• 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.
• Pregnant or breastfeeding females.
• Men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception).
• Patient is simultaneously enrolled in other interventional clinical trial.
• Patient has used an investigational drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
• Patient must not have received prior radiotherapy (except localized palliative radiotherapy for pain, palliation or fracture) within 2 weeks of start of study therapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
• Patient has peripheral neuropathy or neuropathic pain grade 1 with pain or ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
• Patient evidence of cardiovascular risk including any of the following:
• Myocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Uncontrolled cardiac arrhythmia.
• Screening 12-lead ECG showing a baseline interval QTcF\> 470 msec (exception: subjects with pacemaker).

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Bristol-Myers Squibb: collaborator
• Sanofi: collaborator
• Adknoma: collaborator
• Start from scratch: collaborator

Study Sites (68)

Hospital Principe de Asturias

Alcalá de Henares, Madrid, Spain

Location

Hospital Universitario Quirón Salud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Clinica Universidad Navarra (CUN)

Pamplona, Navarre, 31008, Spain

Location

Hospital General Universitario de Albacete

Albacete, Spain

Location

Hospital Germans Trias i Pujol (ICO BADALONA)

Badalona, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari Vall d´Hebron

Barcelona, Spain

Location

ICO L´Hospitalet

Barcelona, Spain

Location

Hospital Universitario de Cruces

Bilbao, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Complejo Hospitalario de Cáceres

Cáceres, Spain

Location

Hospital Universitario de Cabueñes

Gijón, Spain

Location

Hospital Universitari Dr. Josep Trueta (ICO Girona)

Girona, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

Hospital Universitario de Guadalajara

Guadalajara, Spain

Location

H.Universitario de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Complejo Asistencial Universitario de León

León, Spain

Location

Hospital Arnau de Vilanova (Lleida)

Lleida, Spain

Location

Hospital San Pedro

Logroño, Spain

Location

Complejo Hospitalario Lucus Augusti

Lugo, Spain

Location

Fundación Jiménez Díaz-Ute

Madrid, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital HLA Universitario Moncloa

Madrid, Spain

Location

Hospital Universitario 12 de octubre

Madrid, Spain

Location

Hospital Universitario Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario de Fuenlabrada

Madrid, Spain

Location

Hospital Universitario de la Princesa

Madrid, Spain

Location

Hospital Universitario Fundación Alcorcón

Madrid, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario La Zarzuela

Madrid, Spain

Location

Hospital Universitario Puerta del Hierro

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Costa del Sol

Málaga, Spain

Location

Hospital Regional de Málaga

Málaga, Spain

Location

Hospital U Niversitario Virgen de La Victoria

Málaga, Spain

Location

Hospital Universitario Rey Juan Carlos

Móstoles, Spain

Location

H. Morales Meseguer

Murcia, Spain

Location

H. Un. Virgen de la Arrixaca

Murcia, Spain

Location

Hospital General Universitario Santa Lucía

Murcia, Spain

Location

Complejo Hospitalario Universitario de Ourense

Ourense, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Spain

Location

Complejo Hospitalario de Pontevedra

Pontevedra, Spain

Location

Hospital Clinico Universitario Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Spain

Location

Hospital Universitario de Donostia

San Sebastián, Spain

Location

Hospital Universitario Infanta Sofía

San Sebastián de los Reyes, Spain

Location

Complejo Hospitalario Universitario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, Spain

Location

H. Universitario Marqués de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Santiago (CHUS)

Santiago de Compostela, Spain

Location

Hospital General de Segovia

Segovia, Spain

Location

Complejo Hospitalario Regional Virgen Del Rocío

Seville, Spain

Location

H. Universitario de Valme

Seville, Spain

Location

Hospital Universitario Reina Sofía

Seville, Spain

Location

Hospital Universitari de Tarragona Joan XXIII

Tarragona, Spain

Location

Hospital Universitari Mutua Terrassa

Terrassa, Spain

Location

Complejo Hospitalario de Toledo (Virgen de la Salud)

Toledo, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitari i Politecnic la Fe

Valencia, Spain

Location

Hospital Universitario Dr. Peset Aleixandre

Valencia, Spain

Location

H. U. Txagorritxu

Vitoria-Gasteiz, Spain

Location

Hospital Clinico Universitario Lozano Blesa

Zaragoza, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

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  BACKGROUND

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• Amatangelo M, Bjorklund C, Ma P, Wollerman K, Pierceall W, Lonial S, et al. Preclinical and Translational Data Support Development of Iberdomide in Combination with CD38- and SLAMF7-Directed Monoclonal Antibodies: Evidence for Rational Combinations. Blood [Internet]. 2020 Nov 5;136(Supplement 1):9-10. Available from: https://doi.org/10.1182/blood-2020-137667

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• van de Donk NWCJ, Popat R, Larsen J, Minnema MC, Jagannath S, Oriol A, et al. First Results of Iberdomide (IBER; CC-220) in Combination with Dexamethasone (DEX) and Daratumumab (DARA) or Bortezomib (BORT) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM). Blood [Internet]. 2020 Nov 5;136(Supplement 1):16-7. Available from: https://doi.org/10.1182/blood-2020-137743

  BACKGROUND

MeSH Terms

Interventions

Bortezomib; isatuximab; iberdomide; Lenalidomide; Dexamethasone

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Juan José Lahuerta Palacios, Dr

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

• Joan Bladé, Dr

  Hospital Clinic of Barcelona

  STUDY CHAIR

• Mª Victoria Mateos, Dr

  Hospital Clínico Universitario de Salamanca

  STUDY CHAIR

• Enrique M Ocio, Dr

  Hospital Universitario Marqués de Valdecilla

  STUDY CHAIR

• Jesús San Miguel, Dr

  Clínica Universitaria de Navarra

  STUDY CHAIR

Central Study Contacts

Carmen López-Carrero

CONTACT

0034 699 835 437; carmen@fundacionpethema.es

Roberto Maldonado

CONTACT

0034 683 15 66 87; roberto.maldonado@fundacionpethema.es

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2022
• First Posted: September 28, 2022
• Study Start: October 1, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: September 28, 2022

Record last verified: 2022-09

Locations

ES (68)