Multiple MyelomaPhase 3IsKiaNCT04483739
Isa-KRd vs KRd in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation (IsKia TRIAL)
A Phase 3 study testing Carfilzomib Lenalidomide Dexamethasone and Isatuximab Carfilzomib Lenalidomide Dexamethasone in people with Multiple Myeloma, run by European Myeloma Network B.V. at 41 sites in 8 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Carfilzomib Lenalidomide Dexamethasone and Isatuximab Carfilzomib Lenalidomide Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 302 participants
- Where
- 41 sitesin 8 countries
- Study dates
- 25 Sep 2020to 31 Dec 2032
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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:
- Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
- Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
- Life expectancy ≥ 3 months
- ECOG status ≤2
- Clinical laboratory values meeting the following criteria during the Screening Phase:
- Adequate hepatic function, with serum (alanine aminotransferase) ALT ≤ 2.5 times the upper limit of normal (ULN), AST (aspartate transaminase) ≤ 2.5 x the ULN
- Serum direct bilirubin ≤ 1.5 ULN) (except in subjects with congenital bilirubinemia, such as Gilbert syndrome, direct bilirubinemia ≤ 1.5 ULN)
- Absolute neutrophil count (ANC) ≥ 1.0 × 109/L
- Platelet count ≥ 75× 109/L (≥ 50× 109/L if myeloma involvement in the bone marrow is > 50%) and no platelet infusion in the 1 week prior to screening platelet count
- Creatinine clearance (CrCl) ≥ 30 mL/minute. Creatinine clearance should be calculated using eGFR (Modified Diet in Renal Disese [MDRD])
- Corrected serum calcium ≤ 13.5 mg/dL (3.4 mmol/L)
- LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
- Females of childbearing potential (FCBP)* complies with the conditions of the Pregnancy Prevention Plan, including confirmation that she has an adequate level of understanding and must agree to ongoing pregnancy testing and to practice contraception or true abstinence. FCBP must use a highly effective and an additional barrier contraception method simultaneously for 4 weeks before starting therapy, during treatment and dose interruptions and for 5 months after the last dose of study drugs.
- Male subjects must agree to practice contraception if sexually active with FCBP during the treatment and for 5 months after the last dose of study drugs. Males must agree to refrain from donating sperm for at least 90 days after the last dose of carfilzomib and for at least 5 months after the last dose of isatuximab.
- *Note 1: a FCBP is a woman who:
- has achieved menarche at some time point,
- has not undergone a hysterectomy or bilateral oophorectomy or,
- has not 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).
- Note 2: true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Who cannot join
- 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
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- 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
- Pregnant or breastfeeding woman or woman who intends to become pregnant during the participation in the study. FCBP unwilling to prevent pregnancy by the use of 2 reliable methods of contraception for ≥4 weeks before the start of study treatment, during treatment (including dose interruptions), and for at least 28 days following discontinuation of study lenalidomide, or 30 days following discontinuation of carfilzomib or for 5 months after discontinuation of isatuximab treatment, whichever occurs last,
- Male participants who disagree to practice true abstinence or disagree to use a condom during sexual contact with a pregnant woman or a FCBP while participating in the study, during dose interruptions, and for at least 28 days following discontinuation of study lenalidomide, or 30 days following discontinuation of carfilzomib, or for 5 months after discontinuation of isatuximab treatment, whichever occurs last, even if he has undergone a successful vasectomy.
Trial locations and contacts
41 sites in 8 countries.
41 sites in 8 countries
Italy11 sites
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi-SOD Clinica Ematologica
Ancona
University Hospital Consorziale Policlinico-U.O. di Ematologia con Trapianto
Bari
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico - U.O. di Ematologia
Bologna
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia - UOC Ematologia
Brescia
Azienda Ospedaliera Santa Croce E Carle - S.C. Ematologia
Cuneo
Careggi University Hospital - SOD Ematologia
Florence
Azienda Ospedaliero-Universitaria Maggiore Della Carita - SDCU Ematologia
Novara
Fondazione IRCCS Policlinico San Matteo-UOC Ematologia 1
Pavia
Azienda Sanitaria Locale Di Pescara - U.O. Ematologia
Pescara
A.O.U. Città della Salute e della Scienza di Torino-U.O. Ematologia
Torino
Azienda Sanitaria Universitaria Giuliano Isontina-SC U.O.C Ematologia
Trieste
Netherlands11 sites
Noordwest Ziekenhuisgroep Stichting - Internal Medicine - Hematology
Alkmaar
Meander Medisch Centrum -Internal Medicine - Hematology
Amersfoort
Amsterdam-Vrije Universiteit Medical Center (VUMC)
Amsterdam
Amphia Hospital-Internal Medicine - Hematology
Breda
Albert Schweitzerplaats 25
Dordrecht
Zuyderland Medisch Centrum Stichting - Internal Medicine - Hematology
Geleen
Universitair Medisch Centrum Groningen-Department of Haematology
Groningen
Medisch Centrum Leeuwarden B.V. - Oncologisch Centrum Leeuwarden (OCL) and Internal Medicine - Hematology
Leeuwarden
Sint Antonius Ziekenhuis Stichting-Internal Medicine - Hematology
Nieuwegein
ErasmusMC, Rotterdam-Department of Hematology
Rotterdam
Haga Hospital - Internal Medicine - Hematology
s-Gravenweg
Spain7 sites
Hospital Germans Trias I Pujol - Hematology Service ICO Badalona Clinic
Badalona
Hospital Clinic De Barcelona - Myeloma and Amyloidosis Unit
Barcelona
Hospital Universitario 12 De Octubre - Hematology
Madrid
Hospital Universitario 12 De Octubre -Hematology and Hemotherapy Service
Madrid
Clinica Universidad De Navarra - Central Clinical Trials Unit
Pamplona
Hospital Universitario De Salamanca-Department of Hematology of the Salamanca University Care Complex
Salamanca
Hospital Universitario Marques De Valdecilla -Hematology and Hemotherapy Service
Santander
Czechia4 sites
Fakultni Nemocnice Brno - Internal Hematology and Oncology Clinic
Brno
Fakultni Nemocnice Hradec Kralove - 4th Department of Internal Medicine
Nový Hradec Králové
Fakultni Nemocnice Ostrava - Department of Haematooncology
Ostrava
Vseobecna Fakultni Nemocnice V Praze - Internal Medicine, Hematology Clinic
Prague
Germany3 sites
Medical Center - University Of Freiburg - Department Innere Medizin Klinik für Innere Medizin I
Freiburg im Breisgau
University Medical Center Hamburg-Eppendorf - Medizinische Klinik und Polikllinik Onkologie und Knochenmarktransplantation, Haematologie
Hamburg
Klinikum rechts der Isar der TU Muenchen AöR - Innere Medizin III-Haematologie/Onkologie
München
Greece2 sites
Alexandra Hospital - Department of Clinical Therapeutics National & Kapodistrian University of Athens School of Medicine
Athens
Theageneio General Hospital - Department of Hematology Oncology
Thessaloniki
Norway2 sites
Oslo University Hospital HF - Oslo myelomatosesenter
Oslo
St. Olavs Hospital HF - Department of Hematology
Trondheim
Belgium1 site
Het Ziekenhuisnetwerk Antwerpen - Department of Hematology
Antwerp
About this study
Official title: Phase III Study of Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) Versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation (IsKia TRIAL
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.
Read the detailed description
This is a open-label randomized phase III study that enrolls newly diagnosed MM patient eligible for high-dose chemotherapy and ASCT. Patients will be randomized at enrolment (1:1, stratification according to ISS Stage [3 levels: I vs II vs III] and cytogenetic risk FISH [2 levels: high-risk vs standard risk/missing] based on presence of t(4;14), t(14;16), and/or del 17p)) into 2 treatment arms: -ARM A: induction with 4 cycles of Isatuximab-Carfilzomib-Lenalidomide-dexamethasone (Isa-KRd) followed by cyclophophamide and stem cell collections, chemotherapy with Melphalan 200 mg/m2 followed by ASCT (Mel200-ASCT), 4 cycles of Isa-KRd post ASCT consolidation and 12 cycles of Isatuximab-Lenalidomide-Carfilzomib-dexamethasone (IsaKRd) light consolidation; ARM B: induction with 4 cycles of Carfilzomib-Lenalidomide-dexamethasone (KRd) followed by cyclophophamide and stem cell collections, chemotherapy with Melphalan 200 mg/m2 followed by ASCT (Mel200-ASCT), 4 cycles of KRd post ASCT consolidation and 12 cycles of Carfilzomib-Lenalidomide-dexamethasone (KRd) light consolidation. Details of all treatments (dose and schedule) are given in paragraph 8. After light consolidation patients are allowed to receive Lenalidomide maintenance as per standard of care.
- Conditions
- Multiple Myeloma
- Being tested
- Carfilzomib Lenalidomide Dexamethasone, Isatuximab Carfilzomib Lenalidomide Dexamethasone
- Keywords
- newly diagnosed MM, autologous stem cell transplantation, Isatuximab, Carfilzomib, Lenalidomide, Dexamethasone
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carfilzomib Lenalidomide DexamethasoneDrug
Also called KRd
Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation
Isatuximab Carfilzomib Lenalidomide DexamethasoneDrug
Also called Isa-KRD
Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Isatuximab Carfilzomib Lenalidomide Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The end of consolidation, average of 12 months
Secondary outcomes (19)
Post induction MRD negativity rate by NGS
The rate of MRD negativity after induction is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level, NGS) after the induction phase using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment/sample not adequate.
Measured: The end of induction, average of 4 months
Progression-free survival (PFS) in the 2 arms
PFS will be measured from the date of randomization to the date of first observation of PD, or death from any cause as an event. Subjects who have not progressed or who withdraw from the study will be censored at the time of the last complete disease assessment. All subjects who were lost to FU will also be censored at the time of last complete disease assessment
Measured: approximately up to 5 years
Post light-consolidation MRD negativity rate by NGS
The rate of MRD negativity after light consolidation is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level, NGS) after light consolidation phase using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment/sample not adequate. Patients who withdraw from the study or are lost to follow up before MRD evaluation, the best MRD assessment will be considered
Measured: At the end of light-consolidation, average of 24 months
Overall Response Rate (ORR) post-induction
Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after induction.
Measured: Approx 4 months
Overall Response Rate (ORR) post-transplant
Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after ASCT.
Measured: Approximately 8 months
Overall Response Rate (ORR) post-consolidation
Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after consolidation.
Measured: Approximately 12 months
Overall Response Rate (ORR) post light-consolidation
Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after light consolidation.
Measured: Approximately 24 months
Post ASCT MRD negativity rate by NGS
The rate of MRD negativity after ASCT is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level), NGS using ITT principle. For patients who withdraw from the study or are lost to follow up before ASCT, 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.
Measured: After ASCT, approximately 8 months.
MRD negativity rate by NGF post induction
The rate of MRD negativity (by NGF) after induction is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level) after the specific phase using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment. Patients who withdraw from the study or are lost to follow up before MRD evaluation phase, the best MRD assessment will be considered.
Measured: Approximately 4 months
MRD negativity rate by NGF post induction
The rate of MRD negativity (by NGF) after ASCT is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level) after the specific phase using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment. Patients who withdraw from the study or are lost to follow up before MRD evaluation phase, the best MRD assessment will be considered.
Measured: Approximately 8 months
MRD negativity rate by NGF post consolidation
The rate of MRD negativity (by NGF) after consolidation is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level) after the specific phase using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment. Patients who withdraw from the study or are lost to follow up before MRD evaluation phase, the best MRD assessment will be considered.
Measured: Approximately 8 months
MRD negativity rate by NGF post light consolidation
The rate of MRD negativity (by NGF) after light consolidation are determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level) after the specific phase using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment. Patients who withdraw from the study or are lost to follow up before MRD evaluation phase, the best MRD assessment will be considered.
Measured: Approximately 24 months
Duration of response
Duration of response is defined as the time between first documentation of response (achievement of at least a PR) and PD with deaths owning to causes other than progression not counted, but censored. Responders without disease progression at the cut-off date of final analysis will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the at the time of last contact
Measured: approximately up to 9 years
Duration of MRD negativity (by NGS and NGF)
The duration of MRD Negativity (by NGS and NGF) is defined as time between first MRD Negativity and first MRD positivity. Patients without MRD positivity will be censored at last complete assessment
Measured: approximately up to 9 years
Determine the rate of sustained for 1-year MRD negativity (by NGF and NGS) from post ASCT consolidation to post light consolidation
Rate of 1 year sustained MRD negativity by NGS (from post ASCT consolidation to post light consolidation) will be also evaluated.
Measured: approximately up to 9 years
Determine the time to progression (TTP)
From the date of randomization to the date of first disease progression or death per PD, whichever occurs first
Measured: approximately up to 9 years
Overall Survival (OS)
Overall Survival (OS), measured from the date of from randomization to the date the subject's death
Measured: approximately up to 9 years
Time to next therapy (TNT)
TNT will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event. Subjects who have not progressed or who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects lost to FU will also be censored at the time of last contact.
Measured: approximately up to 9 years
Progression-free survival on the next line of therapy (PFS2)
Progression-free survival on the next line of therapy (PFS2) is defined as the time from randomization to progression on the next line of treatment or death, whichever comes first.
Measured: approximately up to 9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2020
- Study start25 Sep 2020
- Primary completion31 Jul 2025
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 302 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Myeloma Network B.V.
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04483739
- Sponsor's protocol ID
- EMN24
- Acronym
- IsKia
- Status last verified
- Jul 2026
- First submitted
- 23 Jun 2020
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Gay F, Roeloffzen W, Dimopoulos MA, Rosinol L, van der Klift M, Mina R, Oriol A, Katodritou E, Wu KL, Rodriguez Otero P, Hajek R, Antonioli E, van Duin M, D'Agostino M, Martinez-Lopez J, van Leeuwen-Segarceanu EM, Zamagni E, van de Donk NWCJ, Weisel KC, Pour L, Radocha J, Belotti A, Schjesvold F, Blade J, Einsele H, Sonneveld P, Boccadoro M, Broijl A. Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial. Nat Med. 2026 May;32(5):1773-1782. doi: 10.1038/s41591-026-04282-0. Epub 2026 Apr 6.
PubMed 41942646
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) Versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation (IsKia TRIAL
- ClinicalTrials.gov ID
- NCT04483739
- Acronym / sponsor ID
- IsKia / EMN24
- Conditions
- Multiple Myeloma
- Keywords
- newly diagnosed MM, autologous stem cell transplantation, Isatuximab, Carfilzomib, Lenalidomide, Dexamethasone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 302 participants (actual)
- Lead sponsor
- European Myeloma Network B.V.Research network
- Collaborators
- EMN Trial Office S.r.l. Impresa Sociale, Sanofi, Amgen
- Study start
- 25 Sep 2020 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 23 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a open-label randomized phase III study that enrolls newly diagnosed MM patient eligible for high-dose chemotherapy and ASCT. Patients will be randomized at enrolment (1:1, stratification according to ISS Stage [3 levels: I vs II vs III] and cytogenetic risk FISH [2 levels: high-risk vs standard risk/missing] based on presence of t(4;14), t(14;16), and/or del 17p)) into 2 treatment arms: -ARM A: induction with 4 cycles of Isatuximab-Carfilzomib-Lenalidomide-dexamethasone (Isa-KRd) followed by cyclophophamide and stem cell collections, chemotherapy with Melphalan 200 mg/m2 followed by ASCT (Mel200-ASCT), 4 cycles of Isa-KRd post ASCT consolidation and 12 cycles of Isatuximab-Lenalidomide-Carfilzomib-dexamethasone (IsaKRd) light consolidation; ARM B: induction with 4 cycles of Carfilzomib-Lenalidomide-dexamethasone (KRd) followed by cyclophophamide and stem cell collections, chemotherapy with Melphalan 200 mg/m2 followed by ASCT (Mel200-ASCT), 4 cycles of KRd post ASCT consolidation and 12 cycles of Carfilzomib-Lenalidomide-dexamethasone (KRd) light consolidation. Details of all treatments (dose and schedule) are given in paragraph 8. After light consolidation patients are allowed to receive Lenalidomide maintenance as per standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Krd Induction | Experimental | Drug: Carfilzomib Lenalidomide Dexamethasone4 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 |
| Isa-KRd induction | Experimental | Drug: Isatuximab Carfilzomib Lenalidomide DexamethasoneIsatuximab= 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 |
| KRd post ASCT consolidation | Experimental | Drug: Carfilzomib Lenalidomide Dexamethasone4 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 |
| Isa-KRd post ASCT consolidation: | Experimental | Drug: Isatuximab Carfilzomib Lenalidomide Dexamethasone4 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 |
| KRd light consolidation | Experimental | Drug: Carfilzomib Lenalidomide Dexamethasone12 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 |
| Isa-KRd light consolidation | Experimental | Drug: Isatuximab Carfilzomib Lenalidomide DexamethasoneIsatuximab= 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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:
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carfilzomib Lenalidomide DexamethasoneAlso: KRdIsatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation | Drug | KRd light consolidation, KRd post ASCT consolidation, Krd Induction |
| Isatuximab Carfilzomib Lenalidomide DexamethasoneAlso: Isa-KRDIsatuximab-Carfilzomib-Lenalidomide-Dexamethasone (Isa-KRd) versus Carfilzomib-Lenalidomide-Dexamethasone (KRd) in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation | Drug | Isa-KRd induction, Isa-KRd light consolidation, Isa-KRd post ASCT consolidation: |
Primary outcome
Rate of MRD negativity after ASCT consolidation treatment by NGS
Time frame: The end of consolidation, average of 12 months
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.
19 secondary outcomes
Post induction MRD negativity rate by NGS
Time frame: The end of induction, average of 4 months
Progression-free survival (PFS) in the 2 arms
Time frame: approximately up to 5 years
Post light-consolidation MRD negativity rate by NGS
Time frame: At the end of light-consolidation, average of 24 months
Overall Response Rate (ORR) post-induction
Time frame: Approx 4 months
Overall Response Rate (ORR) post-transplant
Time frame: Approximately 8 months
Overall Response Rate (ORR) post-consolidation
Time frame: Approximately 12 months
Overall Response Rate (ORR) post light-consolidation
Time frame: Approximately 24 months
Post ASCT MRD negativity rate by NGS
Time frame: After ASCT, approximately 8 months.
MRD negativity rate by NGF post induction
Time frame: Approximately 4 months
MRD negativity rate by NGF post induction
Time frame: Approximately 8 months
MRD negativity rate by NGF post consolidation
Time frame: Approximately 8 months
MRD negativity rate by NGF post light consolidation
Time frame: Approximately 24 months
Duration of response
Time frame: approximately up to 9 years
Duration of MRD negativity (by NGS and NGF)
Time frame: approximately up to 9 years
Determine the rate of sustained for 1-year MRD negativity (by NGF and NGS) from post ASCT consolidation to post light consolidation
Time frame: approximately up to 9 years
Determine the time to progression (TTP)
Time frame: approximately up to 9 years
Overall Survival (OS)
Time frame: approximately up to 9 years
Time to next therapy (TNT)
Time frame: approximately up to 9 years
Progression-free survival on the next line of therapy (PFS2)
Time frame: approximately up to 9 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2026.
- Derived from this study: PubMed 41942646Gay F, Roeloffzen W, Dimopoulos MA, Rosinol L, van der Klift M, Mina R, Oriol A, Katodritou E, Wu KL, Rodriguez Otero P, Hajek R, Antonioli E, van Duin M, D'Agostino M, Martinez-Lopez J, van Leeuwen-Segarceanu EM, Zamagni E, van de Donk NWCJ, Weisel KC, Pour L, Radocha J, Belotti A, Schjesvold F, Blade J, Einsele H, Sonneveld P, Boccadoro M, Broijl A. Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial. Nat Med. 2026 May;32(5):1773-1782. doi: 10.1038/s41591-026-04282-0. Epub 2026 Apr 6.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
41 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Carfilzomib Lenalidomide Dexamethasone and Isatuximab Carfilzomib Lenalidomide Dexamethasone in people with Multiple Myeloma, run by European Myeloma Network B.V. at 41 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in Italy, Netherlands, Spain, Czechia, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of MRD negativity after ASCT consolidation treatment by NGS (time frame: The end of consolidation, average of 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04483739, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2026.