NDMM Patients Candidates for ASCT Comparing Extended VRD Plus vs. Isa-VRD vs. Isa-V-Iberdomide (GEM21menos65)

September 23, 2022 updated by: PETHEMA Foundation

GEM21menos65. A Phase III Trial for NDMM Patients Who Are Candidates for ASCT Comparing Extended VRD Plus Early Rescue Intervention vs Isatuximab-VRD vs Isatuximab-V-Iberdomide-D

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients will receive induction treatment, which will consist: arm A (Isatuximab-VRD + ASCT) or arm B (VRD extended + ASCT plus ERI) or arm C (Isatuximab-VID + ASCT). After ASTC, patients will start consolidation which will be 2 cycles of similar treatment to induction.

Continuous treatment will follow after consolidation and patients will receive:

  • arm A: 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.
  • arm B: after 6 cycles of induction VRD, ASCT and two consolidation VRDs, treatment continues with 10 additional cycles of VRD. During the extension cycles, VRD changes the bortezomib and dexamethasone regimen. In these10 cycles, both bortezomib and dexamethasone will be administered, at the same doses as the previous ones, but on a weekly schedule, on days 1, 8, 15 and 22 of each cycle. The lenalidomide regimen remains unchanged.
  • arm C: 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.

The primary objective is to compare the efficacy of extended VRD + ASCT plus ERI (Arm B) vs. Isatuximab-VRD + ASCT (Arm A) in terms of proportion of patients who are MRD-negative by next generation flow cytometry (NGF) after 18 cycles + ASCT.

The primary endpoint, the MRD rate, takes as a reference the evaluation after the last extended VRD cycle, this is: 6 cycles for induction, 6 months for transplantation, 2 cycles for consolidation and 10 cycles until completing the 18 cycles of VRD, (in total about 24 months). For this reason,the primary endpoint in Arms A and C are established after a similar treatment time, which includes 4 cycles of induction, ASCT, 2 cycles of consolidation and 12 cycles of continuous treatment with Iberdomide plus Isatuximab (Dexamethasone to be determined).In patients of Arm B included in ERI, due to the great variability of the possible moments of incorporation in this therapeutic program, only rules are established for the moment and the realization or not of the transplant. The evaluation of the results will be carried out separately in the patients included, butalso in conjunction with the rest of the patients in Arm B to know the effect of the global strategy.

After the evaluation of the primary endpoint, continuous/maintenance treatment continues in Arms A, B and C, including patients in ARM B assigned to the ERI program. Obtaining conventional CR in either arm will require a BM analysis for MRD. In the case of stable response or improvement without RC, MRD controls have been pre-established. Due to the lack of data on tolerance and adherence to long-term treatment with Isatuximab and Iberdomide, changes in the therapeutic programs, for this reason, a complete revision of the therapeutic program has been predetermined at the moment in which the last patient included in the clinical trial reaches 36 months of treatment. At this point, taking into account the updated knowledge about continuous or maintenance treatments, the strategies for a second clinical trial or an extension of this clinical trial will be defined.

Study Type

Interventional

Enrollment (Anticipated)

480

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Albacete, Spain
      • Badalona, Spain
        • Hospital Germans Trias i Pujol (ICO BADALONA)
        • Contact:
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
        • Contact:
        • Principal Investigator:
          • Miguel Granell Gorrochategui
      • Barcelona, Spain
        • Hospital Clinic i Provincial de Barcelona
        • Principal Investigator:
          • Laura Rosiñol
        • Contact:
      • Barcelona, Spain
      • Barcelona, Spain
        • ICO L´Hospitalet
        • Contact:
        • Principal Investigator:
          • Anna Sureda Balari
      • Bilbao, Spain
      • Burgos, Spain, 09006
        • Hospital Universitario de Burgos
        • Contact:
        • Principal Investigator:
          • Francisco Javier Díaz Gálvez
      • Cáceres, Spain
        • Complejo Hospitalario de Caceres
        • Contact:
        • Principal Investigator:
          • Ignacio Casas Avilés
      • Gijón, Spain
        • Hospital Universitario de Cabueñes
        • Contact:
        • Principal Investigator:
          • Maria Esther Gonzalez Garcia
      • Girona, Spain
        • Hospital Universitari Dr. Josep Trueta (ICO Girona)
        • Contact:
      • Granada, Spain
        • Hospital Universitario Virgen de las Nieves
        • Contact:
        • Principal Investigator:
          • Maria Esther Clavero Sanchez
      • Guadalajara, Spain
        • Hospital Universitario de Guadalajara
        • Contact:
        • Principal Investigator:
          • Dunia de Miguel Llorente
      • Jerez De La Frontera, Spain
      • La Laguna, Spain
      • León, Spain
        • Complejo Asistencial Universitario de León
        • Contact:
        • Principal Investigator:
          • Fernando Escalante Barrigon
      • Lleida, Spain
        • Hospital Arnau de Vilanova (Lleida)
        • Contact:
        • Principal Investigator:
          • Antoni García Guiñón
      • Logroño, Spain
        • Hospital San Pedro
        • Contact:
        • Principal Investigator:
          • María José Nájera Irazu
      • Lugo, Spain
        • Complejo Hospitalario Lucus Augusti
        • Contact:
        • Principal Investigator:
          • Esperanza Lavilla Rubia
      • Madrid, Spain
        • Hospital General Universitario Gregorio Maranon
        • Contact:
        • Principal Investigator:
          • Cristina Encinas Rodríguez
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
        • Principal Investigator:
          • Joaquín Martínez López
        • Contact:
      • Madrid, Spain
      • Madrid, Spain
        • Hospital Universitario La Paz
        • Contact:
        • Principal Investigator:
          • Ana López de la Guía
      • Madrid, Spain
      • Madrid, Spain
        • Hospital Universitario Ramon Y Cajal
        • Contact:
        • Principal Investigator:
          • María Jesús Blanchard Rodríguez
      • Madrid, Spain
      • Madrid, Spain
        • Hospital Universitario Puerta del Hierro
        • Contact:
        • Principal Investigator:
          • Rafael Ríos Tamayo
      • Madrid, Spain
        • Fundacion Jimenez Diaz-UTE
        • Contact:
        • Principal Investigator:
          • Elena Prieto Pareja
      • Madrid, Spain
      • Madrid, Spain
      • Madrid, Spain
        • Hospital HLA Universitario Moncloa
        • Contact:
        • Principal Investigator:
          • María Concepción Alaez Usón
      • Madrid, Spain
        • Hospital Universitario Hm Sanchinarro
        • Contact:
        • Principal Investigator:
          • Jaime Perez de Oteyza
      • Madrid, Spain
        • Hospital Universitario la Zarzuela
        • Contact:
        • Principal Investigator:
          • Daniel García Belmonte
      • Murcia, Spain
        • H. Morales Meseguer
        • Contact:
        • Principal Investigator:
          • Felipe De Arriba de la Fuente
      • Murcia, Spain
        • H. Un. Virgen de la Arrixaca
        • Contact:
        • Principal Investigator:
          • Valentín Cabañas Perianes
      • Murcia, Spain
        • Hospital General Universitario Santa Lucia
        • Principal Investigator:
          • Marta Romera Martínez
        • Contact:
      • Málaga, Spain
        • Hospital Regional de Malaga
        • Contact:
        • Principal Investigator:
          • Maria Magdalena Alcala Pena
      • Málaga, Spain
        • Hospital Costa del Sol
        • Contact:
        • Principal Investigator:
          • María Casanova Espinosa
      • Málaga, Spain
        • Hospital U Niversitario Virgen de La Victoria
        • Principal Investigator:
          • Ricarda Garcia Sanchez
        • Contact:
      • Móstoles, Spain
      • Ourense, Spain
        • Complejo Hospitalario Universitario de Ourense
        • Contact:
        • Principal Investigator:
          • José Angel Méndez Sánchez
      • Oviedo, Spain
      • Palma De Mallorca, Spain
        • Hospital Son Llatzer
        • Contact:
        • Principal Investigator:
          • Joan Bargay Llenonart
      • Palma De Mallorca, Spain
        • Hospital Universitari Son Espases
        • Contact:
        • Principal Investigator:
          • Antonia Sampol Mayol
      • Pamplona, Spain
        • Complejo Hospitalario de Navarra
        • Contact:
        • Principal Investigator:
          • Jose Maria Arguiñano Perez
      • Pontevedra, Spain
        • Complejo Hospitalario de Pontevedra
        • Contact:
        • Principal Investigator:
          • Ana Maria Dios Loureiro
      • Salamanca, Spain, 37007
        • Hospital Clinico Universitario Salamanca
        • Contact:
        • Principal Investigator:
          • Mª Victoria Mateos Manteca
      • San Sebastián, Spain
        • Hospital Universitario de Donostia
        • Contact:
        • Principal Investigator:
          • Maialen Sirvent Auzmendi
      • San Sebastián De Los Reyes, Spain
        • Hospital Universitario Infanta Sofía
        • Contact:
        • Principal Investigator:
          • Eugenio Giménez Mesa
      • Santa Cruz De Tenerife, Spain
        • Complejo Hospitalario Universitario Nuestra Señora de la Candelaria
        • Contact:
        • Principal Investigator:
          • Pablo Ríos Rull
      • Santander, Spain
        • H. Universitario Marqués de Valdecilla
        • Principal Investigator:
          • Enrique Ocio
        • Contact:
      • Santiago De Compostela, Spain
      • Segovia, Spain
        • Hospital General de Segovia
        • Contact:
        • Principal Investigator:
          • Aránzazu García Mateo
      • Sevilla, Spain
        • Complejo Hospitalario regional Virgen del Rocio
        • Contact:
        • Principal Investigator:
          • Estrella Carrillo Cruz
      • Sevilla, Spain
      • Sevilla, Spain
      • Tarragona, Spain
        • Hospital Universitari de Tarragona Joan XXIII
        • Contact:
        • Principal Investigator:
          • Josep Sarrà Escarré, Dr
      • Terrassa, Spain
        • Hospital Universitari Mútua Terrassa
        • Contact:
        • Principal Investigator:
          • Josep Mª Martí Tutusaus
      • Toledo, Spain
        • Complejo Hospitalario de Toledo (Virgen de la Salud)
        • Principal Investigator:
          • Felipe Casado Montero
        • Contact:
      • Valencia, Spain
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain
        • Hospital Universitari i Politecnic La Fe
        • Contact:
        • Principal Investigator:
          • Mario Arnao Herraiz
      • Valencia, Spain
        • Hospital Universitario Dr. Peset Aleixandre
        • Contact:
        • Principal Investigator:
          • Paz Ribas García
      • Vitoria, Spain
      • Zaragoza, Spain
        • Hospital Universitario Miguel Servet
        • Contact:
        • Principal Investigator:
          • Ana Cristina Godoy Molias
      • Zaragoza, Spain
        • Hospital Clínico Universitario Lozano Blesa
        • Contact:
        • Principal Investigator:
          • Luis Ramón Palomera Bernal
    • Madrid
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universidad Navarra (CUN)
        • Contact:
        • Principal Investigator:
          • Jesús San Miguel Izquierdo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
  2. Patient must be able to understand the study procedures.
  3. 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.
  4. 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].
  5. 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.
  6. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  7. Patient must be ≤ 65 years of age.

  8. 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
    • Renal: eGFRa: ≥40 mL/min/ 1.73 m2
    • Cardiac: LVEF (echo) ≥ 50%

  9. Female patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    • Is not a woman of childbearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy OR

    • Is a WOCBP and

      • She understands the potential teratogenic risk to the unborn child
      • She understands the need for effective contraception as stated in the protocol, without interruption, 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions and for at least 28 days after the last dose of study treatment.
      • She understands and agrees to inform the Investigator if a change or stop of method of contraception is needed.
      • She must be capable of complying with effective contraceptive measures.
      • She is informed and understands the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.
      • She understands the need to commence study treatment as soon as it is dispensed following a negative pregnancy test.
      • She understands and accepts the need to undergo pregnancy testing based on the frequency outlined in this plan and in the Informed Consent.
      • She acknowledges she understands the hazards iberdomide or lenalidomide can cause to an unborn fetus and the necessary precautions associated with the use of study drugs.

    The Investigator must ensure that a WOCBP: i) Complies with the conditions of the pregnancy prevention plan, including confirmation that she has an adequate level of understanding. ii) Acknowledges the aforementioned requirements.

    A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study drug.

    Nonchildbearing potential is defined as follows (by other than medical reasons):

    • Has not achieved menarche at some point.
    • Has undergone a hysterectomy or bilateral oophorectomy.
    • Has been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).

  10. Male patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    Male patient is eligible to participate if he agrees to the following from the time of first dose of study until 6 months after the last dose of iberdomide or lenalidomide to allow for clearance of any altered sperm:

    • Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a WOCBP.
    • Understand the need for the use of a condom even if he has had a vasectomy, if engaged in sexual activity with a pregnant female or a FCBP
    • Understand the potential teratogenic risk, so the subject should not donate semen or sperm.. Understand that the effects on fertility are currently unknown, therefore all family planning options and/or alternatives should be thoroughly discussed with the study doctor prior to receiving iberdomide.
  11. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia.

Exclusion Criteria:

  1. 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.
  2. Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma.
  3. 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.
  4. 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.
  5. Pregnant or breastfeeding females.
  6. Men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception).
  7. Patient is simultaneously enrolled in other interventional clinical trial.
  8. Patient has used an investigational drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
  9. 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.
  10. Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
  11. 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.

  12. 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).
    • Patients with uncontrolled hypertension.
  13. Patients who have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
  14. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient's safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria.
  15. Evidence of active mucosal or internal bleeding.
  16. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
  17. Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
  18. Patient with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
  19. Patient with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
  20. History of interstitial lung disease or ongoing interstitial lung disease.
  21. Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment.
  22. Patient has an active infection requiring systemic antibiotic, antiviral, or antifungal treatment at the time of starting treatment.
  23. Patient has known HIV infection.
  24. Patient has positive hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study treatment.
  25. Patient has positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required.
  26. Patient require concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment).
  27. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to iberdomide or drugs chemically related to iberdomide.
  28. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to isatuximab or drugs chemically related to isatuximab, hypersensitivity reactions, or idiosyncratic reactions to other molecular antibodies.
  29. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to lenalidomide or dexamethasone or drugs chemically related to lenalidomide or dexamethasone.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control arm (A)

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: Dexamethasone
Dexamethasone
Drug: Lenalidomide
Lenalidomide
Drug: Bortezomib
Bortezomib
Drug: Isatuximab
Isatuximab
Experimental: EXPERIMENTAL ARM (B): Extended VRD and Early Rescue Intervention

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: Dexamethasone
Dexamethasone
Drug: Lenalidomide
Lenalidomide
Drug: Bortezomib
Bortezomib
Drug: Isatuximab
Isatuximab
Drug: Iberdomide
Iberdomide
Experimental: EXPLORATORY ARM (C)

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy in terms of patients who are MRD-negative by NGF
Time Frame: 24 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of adverse events (AEs)
Time Frame: Throughout the study. Approximately 78 months.
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.
Throughout the study. Approximately 78 months.
Progression-Free Survival (PFS)
Time Frame: Throughout the study. Approximately 78 months
Time from the start of treatment until the earliest date of documented disease progression or death due to any cause.
Throughout the study. Approximately 78 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Throughout the study. Approximately 78 months
Percentage of participants with a confirmed partial response (PR) or better (PR, VGPR, CR, sCR).
Throughout the study. Approximately 78 months
Complete Response Rate (CRR)
Time Frame: Throughout the study. Approximately 78 months
The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR)).
Throughout the study. Approximately 78 months
Time to Response (TTR)
Time Frame: Throughout the study. Approximately 78 months
Time from the start of treatment and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better.
Throughout the study. Approximately 78 months
Duration of Response (DoR)
Time Frame: Throughout the study. Approximately 78 months
Time from first documented evidence of PR or better until progressive disease (PD) or death due to PD among participants who achieved PR or better.
Throughout the study. Approximately 78 months
Overall Survival (OS)
Time Frame: Throughout the study. Approximately 78 months
Time from the start of treatment until the date of death due to any cause
Throughout the study. Approximately 78 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Collaborators

Bristol-Myers Squibb
Sanofi
Adknoma
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Investigators

  • Study Chair: 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 Clinico Universitario de Salamanca
  • Study Chair: Enrique M Ocio, Dr, Hospital Universitario Marqués de Valdecilla
  • Study Chair: Jesús San Miguel, Dr, Clinica Universitaria de Navarra

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2022

Primary Completion (Anticipated)

April 1, 2027

Study Completion (Anticipated)

April 1, 2029

Study Registration Dates

First Submitted

September 23, 2022

First Submitted That Met QC Criteria

September 23, 2022

First Posted (Actual)

September 28, 2022

Study Record Updates

Last Update Posted (Actual)

September 28, 2022

Last Update Submitted That Met QC Criteria

September 23, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEM21menos65

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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