Isa-KRd vs KRd in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation (IsKia TRIAL)

NCT04483739 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: EMN24
• Study Type: interventional
• Target: 302
• Locations: 8 countries
• Sites: 41

Brief Summary

This protocol is a phase III study designed to compare the efficacy and the safety of Isa-KRd induction, transplant, Isa-KRd post ASCT consolidation and Isa-KRd light consolidation vs KRd induction, transplant, KRd post ASCT consolidation and KRd light consolidation After confirmation of eligibility criteria patients will be randomized to one of the 2 treatment groups in a 1:1 randomization ratio.

Conditions

Multiple Myeloma

Keywords

newly diagnosed MM; autologous stem cell transplantation; Isatuximab; Carfilzomib; Lenalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (1)

• Rate of MRD negativity after ASCT consolidation treatment by NGS

  The rate of MRD negativity is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level) after ASCT consolidation treatment using ITT principle. For patients who withdraw from the study or are lost to follow up before four post ASCT consolidation cycles, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.

  The end of consolidation, average of 12 months

Secondary Outcomes (19)

• Post induction MRD negativity rate by NGS

  The end of induction, average of 4 months

• Progression-free survival (PFS) in the 2 arms

  approximately up to 5 years

• Post light-consolidation MRD negativity rate by NGS

  At the end of light-consolidation, average of 24 months

• Overall Response Rate (ORR) post-induction

  Approx 4 months

• Overall Response Rate (ORR) post-transplant

  Approximately 8 months

Study Arms (6)

Krd Induction

EXPERIMENTAL

4 28 day cycles of Carfilzomib = 20 mg/m2 IV on day 1 cycle 1 only, followed by 56 mg/m2 IV on days 8, 15 cycle 1 and on days 1, 8, 15 for cycles 2-4 Lenalidomide= 25 mg orally daily on days 1-21 Dexamethasone = 40 mg orally/IV on days 1, 8, 15, 22

Drug: Carfilzomib Lenalidomide Dexamethasone

Isa-KRd induction

EXPERIMENTAL

Isatuximab= 10 mg/kg IV on day 1, 8, 15, and 22 during Cycle 1, followed by 10 mg/kg IV on days 1 and 15 during Cycles 2 to 4. Carfilzomib = 20 mg/m2 IV on day 1 cycle 1 only, followed by 56 mg/m2 IV on days 8, 15 cycle 1 and on days 1, 8, 15 for cycles 2-4 Lenalidomide= 25 mg orally daily on days 1-21 Dexamethasone = 40 mg orally/IV on days 1, 8, 15, 22

Drug: Isatuximab Carfilzomib Lenalidomide Dexamethasone

KRd post ASCT consolidation

EXPERIMENTAL

4 28 day cycles of Carfilzomib = 56 mg/m2 IV on days 1, 8, 15 cycle 5-8 Lenalidomide= 25 mg orally daily on days 1-21 Dexamethasone = 40 mg orally/IV on days 1, 8, 15, 22

Drug: Carfilzomib Lenalidomide Dexamethasone

Isa-KRd post ASCT consolidation:

EXPERIMENTAL

4 28 day cycles of Isatuximab= 10 mg/kg IV on days 1 and 15 on cycles 5-8 Carfilzomib = 56 mg/m2 IV on days 1, 8, 15 cycle 5-8 Lenalidomide= 25 mg orally daily on days 1-21 Dexamethasone = 40 mg orally/IV on days 1, 8, 15, 22

Drug: Isatuximab Carfilzomib Lenalidomide Dexamethasone

KRd light consolidation

EXPERIMENTAL

12 28 day cycles of Carfilzomib = 56 mg/m2 IV on days 1, 15 Lenalidomide = 10 mg orally on days 1-21 Dexamethasone = 20 mg orally/IV on days 1, 15

Drug: Carfilzomib Lenalidomide Dexamethasone

Isa-KRd light consolidation

EXPERIMENTAL

Isatuximab= 10 mg/kg IV on day 1 Carfilzomib = 56 mg/m2 IV on days 1, 15 Lenalidomide = 10 mg orally on days 1-21 Dexamethasone = 20 mg orally/IV on days 1, 15

Drug: Isatuximab Carfilzomib Lenalidomide Dexamethasone

Interventions

Carfilzomib Lenalidomide Dexamethasone DRUG

Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation

Also known as: KRd

KRd light consolidation; KRd post ASCT consolidation; Krd Induction

Isatuximab Carfilzomib Lenalidomide Dexamethasone DRUG

Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation

Also known as: Isa-KRD

Isa-KRd induction; Isa-KRd light consolidation; Isa-KRd post ASCT consolidation:

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with newly diagnosed multiple myeloma and eligible to ASCT.
• Patient is, in the investigator's opinion, willing and able to comply with the study visits and procedures required per protocol.
• Patient has provided written informed consent in accordance with federal, local, and institutional guidelines prior to initiation of any study-specific activities or procedures. Subject does not have kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
• Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:
• CRAB criteria:
• Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL)
• Renal insufficiency: creatinine clearance \<40mL/min or serum creatinine \>177 μmol/L (\>2 mg/dL)
• Anemia: hemoglobin \>2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
• Biomarkers of Malignancy:
• Clonal bone marrow plasma cell percentage ≥60%
• Involved: uninvolved serum FLC ratio ≥100
• \>1 focal lesion on magnetic resonance imaging (MRI) studies
• Patient is 18 - 70 years old and is eligible for autologous stem cell transplantation
• Patient has measurable disease as defined by any one of the following:

You may not qualify if:

• Previous treatment with anti-myeloma therapy (does not include radiotherapy, biphosphonates, or a single short course of steroid ≤ to the equivalent of dexamethasone 40 mg/day for 4 days).
• Patients with non-secretory MM unless serum free light chains are present and the ratio is abnormal or a plasmacytoma with minimum largest diameters of \> 2 cm.
• Patients with plasma cell leukemia, amyloidosis, Waldenstrom Disease, POEMS syndrome
• Meningeal involvement of multiple myeloma
• Patient ineligible for autologous transplantation
• Pregnant or lactating females
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
• Known human immunodeficiency virus infection (HIV)
• Active hepatitis A, B or C infection. Hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy are allowed). Tests to be performed if required per local country regulations. In fact it is not possible to avoid the risk of virological reactivation with the study treatments.
• Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, (Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology 2013 guidelines), pulmonary embolia, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
• Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization as defined by National Cancer Institute Common Toxicity Criteria (NCI CTCAE) 5.0
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) and to PS80; prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), or any of the components (active substance or excipients) of study treatments that are not amenable to premedication with steroids, or H2 blockers, that would prohibit further treatment with these agents.
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
• Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Sponsors & Collaborators

• European Myeloma Network B.V.: lead
• EMN Trial Office S.r.l. Impresa Sociale: collaborator
• Sanofi: collaborator
• Amgen: collaborator

Study Sites (41)

Het Ziekenhuisnetwerk Antwerpen - Department of Hematology

Antwerp, Belgium

Location

Fakultni Nemocnice Brno - Internal Hematology and Oncology Clinic

Brno, Czechia

Location

Fakultni Nemocnice Hradec Kralove - 4th Department of Internal Medicine

Nový Hradec Králové, Czechia

Location

Fakultni Nemocnice Ostrava - Department of Haematooncology

Ostrava, Czechia

Location

Vseobecna Fakultni Nemocnice V Praze - Internal Medicine, Hematology Clinic

Prague, Czechia

Location

Medical Center - University Of Freiburg - Department Innere Medizin Klinik für Innere Medizin I

Freiburg im Breisgau, Germany

Location

University Medical Center Hamburg-Eppendorf - Medizinische Klinik und Polikllinik Onkologie und Knochenmarktransplantation, Haematologie

Hamburg, Germany

Location

Klinikum rechts der Isar der TU Muenchen AöR - Innere Medizin III-Haematologie/Onkologie

München, Germany

Location

Alexandra Hospital - Department of Clinical Therapeutics National & Kapodistrian University of Athens School of Medicine

Athens, Greece

Location

Theageneio General Hospital - Department of Hematology Oncology

Thessaloniki, Greece

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi-SOD Clinica Ematologica

Ancona, Italy

Location

University Hospital Consorziale Policlinico-U.O. di Ematologia con Trapianto

Bari, Italy

Location

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico - U.O. di Ematologia

Bologna, Italy

Location

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia - UOC Ematologia

Brescia, Italy

Location

Azienda Ospedaliera Santa Croce E Carle - S.C. Ematologia

Cuneo, Italy

Location

Careggi University Hospital - SOD Ematologia

Florence, Italy

Location

Azienda Ospedaliero-Universitaria Maggiore Della Carita - SDCU Ematologia

Novara, Italy

Location

Fondazione IRCCS Policlinico San Matteo-UOC Ematologia 1

Pavia, Italy

Location

Azienda Sanitaria Locale Di Pescara - U.O. Ematologia

Pescara, Italy

Location

A.O.U. Città della Salute e della Scienza di Torino-U.O. Ematologia

Torino, Italy

Location

Azienda Sanitaria Universitaria Giuliano Isontina-SC U.O.C Ematologia

Trieste, Italy

Location

Noordwest Ziekenhuisgroep Stichting - Internal Medicine - Hematology

Alkmaar, Netherlands

Location

Meander Medisch Centrum -Internal Medicine - Hematology

Amersfoort, Netherlands

Location

Amsterdam-Vrije Universiteit Medical Center (VUMC)

Amsterdam, Netherlands

Location

Amphia Hospital-Internal Medicine - Hematology

Breda, Netherlands

Location

Albert Schweitzerplaats 25

Dordrecht, Netherlands

Location

Zuyderland Medisch Centrum Stichting - Internal Medicine - Hematology

Geleen, Netherlands

Location

Universitair Medisch Centrum Groningen-Department of Haematology

Groningen, Netherlands

Location

Medisch Centrum Leeuwarden B.V. - Oncologisch Centrum Leeuwarden (OCL) and Internal Medicine - Hematology

Leeuwarden, Netherlands

Location

Sint Antonius Ziekenhuis Stichting-Internal Medicine - Hematology

Nieuwegein, Netherlands

Location

ErasmusMC, Rotterdam-Department of Hematology

Rotterdam, Netherlands

Location

Haga Hospital - Internal Medicine - Hematology

s-Gravenweg, Netherlands

Location

Oslo University Hospital HF - Oslo myelomatosesenter

Oslo, Norway

Location

St. Olavs Hospital HF - Department of Hematology

Trondheim, Norway

Location

Hospital Germans Trias I Pujol - Hematology Service ICO Badalona Clinic

Badalona, Spain

Location

Hospital Clinic De Barcelona - Myeloma and Amyloidosis Unit

Barcelona, Spain

Location

Hospital Universitario 12 De Octubre - Hematology

Madrid, Spain

Location

Hospital Universitario 12 De Octubre -Hematology and Hemotherapy Service

Madrid, Spain

Location

Clinica Universidad De Navarra - Central Clinical Trials Unit

Pamplona, Spain

Location

Hospital Universitario De Salamanca-Department of Hematology of the Salamanca University Care Complex

Salamanca, Spain

Location

Hospital Universitario Marques De Valdecilla -Hematology and Hemotherapy Service

Santander, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: July 23, 2020
• Study Start: September 25, 2020
• Primary Completion: July 31, 2025
• Study Completion (Estimated): December 31, 2032
• Last Updated: February 26, 2025

Record last verified: 2025-02

Locations

ES (7); CZ (4); NO (2); DE (3); BE (1); IT (11); GR (2); NL (11)