MInimal Residual Disease Adapted Strategy
MIDAS
2 other identifiers
interventional
791
3 countries
73
Brief Summary
IFM 2020-02 will enroll patients eligible for ASCT less than 66 years. All patients will receive induction based on 6 cycles (28-day) of KRD-Isatuximab (Isa-KRD), in order to achieve deep responses and high MRD negativity rates. Patients will be classified at diagnosis according to cytogenetics (standard vs high-risk cytogenetics defined by the LP score including 17p deletion, t(4;14), del(1p32), gain 1q, trisomy 21 and trisomy 5).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-myeloma
Started Dec 2021
Typical duration for phase_3 multiple-myeloma
73 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 11, 2021
CompletedFirst Posted
Study publicly available on registry
June 22, 2021
CompletedStudy Start
First participant enrolled
December 8, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
September 30, 2028
ExpectedNovember 7, 2024
November 1, 2024
2.8 years
May 11, 2021
November 5, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Negative MRD rate
For both parts of the trial (A vs B and C vs D), the primary comparison of the 2 strategies will be made with respect to negative MRD rate (10-6 NGS) before maintenance using the chi square test in the ITT population. The observed MRD negative rate will be provided along with its 2-sided 95% Confidence interval (CI). Treatment effect will be described by an Odds Ratio, along with its 2-sided 95% confidence interval, by fitting a logistic regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). In case of missing MRD, data will be imputed as positive in all arms. Sensitivity analyses will be performed using best-worst and worst-best case to check for robustness of the results.
Time Frame: change from post induction baseline MRD at end of consolidation phase (6 months)
Negative MRD rate
For both parts of the trial (A vs B and C vs D), the primary comparison of the 2 strategies will be made with respect to negative MRD rate (10-6 NGS) before maintenance using the chi square test in the ITT population. The observed MRD negative rate will be provided along with its 2-sided 95% Confidence interval (CI). Treatment effect will be described by an Odds Ratio, along with its 2-sided 95% confidence interval, by fitting a logistic regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). In case of missing MRD, data will be imputed as positive in all arms. Sensitivity analyses will be performed using best-worst and worst-best case to check for robustness of the results.
change from post induction baseline MRD at 1 years
Negative MRD rate
For both parts of the trial (A vs B and C vs D), the primary comparison of the 2 strategies will be made with respect to negative MRD rate (10-6 NGS) before maintenance using the chi square test in the ITT population. The observed MRD negative rate will be provided along with its 2-sided 95% Confidence interval (CI). Treatment effect will be described by an Odds Ratio, along with its 2-sided 95% confidence interval, by fitting a logistic regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). In case of missing MRD, data will be imputed as positive in all arms. Sensitivity analyses will be performed using best-worst and worst-best case to check for robustness of the results.
change from post induction baseline MRD at 2 years
Negative MRD rate
For both parts of the trial (A vs B and C vs D), the primary comparison of the 2 strategies will be made with respect to negative MRD rate (10-6 NGS) before maintenance using the chi square test in the ITT population. The observed MRD negative rate will be provided along with its 2-sided 95% Confidence interval (CI). Treatment effect will be described by an Odds Ratio, along with its 2-sided 95% confidence interval, by fitting a logistic regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). In case of missing MRD, data will be imputed as positive in all arms. Sensitivity analyses will be performed using best-worst and worst-best case to check for robustness of the results.
change from post induction baseline MRD at 3 years
Secondary Outcomes (7)
Sustained MRD rate
change from post induction baseline MRD at end of consolidation phase (6 months)
Sustained MRD rate
change from post induction baseline MRD at 1 years
Sustained MRD rate
change from post induction baseline MRD at 2 years
Sustained MRD rate
change from post induction baseline MRD at 3 years
Overall Survival (OS)
through study completion, an average of 8 year
- +2 more secondary outcomes
Study Arms (4)
MRD Standard-risk patients (post induction MRD <10-5, MRD SR) (1:1 Randomization) : Arm A
EXPERIMENTALArm A: consolidation with 6 additional cycles of Isa-KRD (cycles 7 to 12; 28-day cycle; Isa-KRD = Isatuximab Carfilzomib Lenalidomide Dexamethasone): * Isatuximab: 10 mg/kg I.V. on days 1 and 15 (cycles 7 to 12) * Carfilzomib: 56 mg/m2 I.V on days 1, 8 and 15 (cycles 7 to 12) * Lenalidomide: 25 mg per day orally from days 1 to 21 * Dexamethasone: 40 mg orally on day 1, 8, 15, 22
MRD Standard-risk patients (post induction MRD <10-5, MRD SR) (1:1 Randomization): Arm B
EXPERIMENTALArm B: consolidation with ASCT followed by 2 cycles of Isa-KRD (cycles 7 and 8; Isa-KRD = Isatuximab Carfilzomib Lenalidomide Dexamethasone; 28-day cycle) Melphalan 200 mg/m2 followed by autologous stem cell transplantation (please refer to section 6.3.2) * Isatuximab: 10 mg/kg I.V. on days 1 and 15 (cycles 7 to 8) * Carfilzomib: 56 mg/m2 I.V on days on days 1, 8 and 15 (cycles 7 to 8) * Lenalidomide: 25 mg per day orally from days 1 to 21 * Dexamethasone: 40 mg orally on days 1, 8, 15, 22 (cycles 7 to 8)
MRD High-risk patients (post induction MRD >10-5, MRD HR) (1:1 Randomization): Arm C
EXPERIMENTALArm C: ASCT followed by 2 cycles of Isa-KRD (cycles 7 and 8; Isa-KRD = Isatuximab Carfilzomib Lenalidomide Dexamethasone; 28-day cycle) Melphalan 200 mg/m2 followed by autologous stem cell transplantation. * Isatuximab: 10 mg/kg I.V. on days 1 and 15 (cycles 7 to 8) * Carfilzomib: 56 mg/m2 I.V on days on days 1, 8 and 15 (cycle 7 to 8) * Lenalidomide: 25 mg per day orally from day 1 to day 21 * Dexamethasone: 40 mg orally on days 1, 8, 15, 22 (cycle 7 to 8)
MRD High-risk patients (post induction MRD >10-5, MRD HR) (1:1 Randomization): Arm D
EXPERIMENTALTandem ASCT Melphalan 200 mg/m2 followed by autologous stem cell transplantation.
Interventions
Treatment with Isa-KRD during induction and consolidation , with Lenalidomide (Revlimid) or Iberdomide + Isatuximab during maintenance phase
ASCT for ams B, C and D during consolidation
Eligibility Criteria
You may qualify if:
- Male or female subjects, 18 years of age or older, younger than 66 years (\< 66 years)
- Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
- Subject must have documented multiple myeloma satisfying the CRAB and measurable disease as defined by:
- Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma AND any one or more of the following myeloma defining events:
- Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than 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
- Clonal bone marrow plasma cell percentage ≥ 60%
- Involved: uninvolved serum free light chain ratio ≥ 100
- Superior 1 focal lesion on MRI studies
- Measurable disease as defined by the following:
- M-component ≥ 5g/L, and/or urine M-component ≥ 200 mg/24h and/or serum FLC ≥ 100 mg/L
- Newly diagnosed subjects eligible for high dose therapy and autologous stem cell transplantation
- Karnofsky performance status score ≥ 50% (eastern cooperative oncology group performance status ECOG score ≤ 2)
- +11 more criteria
You may not qualify if:
- Subjects must not have been treated previously with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify the subject (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in a 2-week period). Two weeks must have elapsed since the date of the last radiotherapy treatment. Enrolment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
- Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
- Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
- Subject has had plasmapheresis within 14 days of C1D1.
- Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
- Myocardial infarction within 4 months prior to enrolment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Uncontrolled hypertension
- Subjects with a history of moderate or severe persistent asthma within the past 2 years, or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
- Intolerance to hydration due to pre-existing pulmonary or cardiac impairment.
- Subject has plasma cell leukemia (according to WHO criterion: ≥ 20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results.
- Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment.
- Known intolerance to steroid therapy, mannitol, pregelatinized starch, odium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
- History of allergy to any of the study medications, their analogues, or excipients in the various formulations
- Clinically relevant active infection or serious co-morbid medical conditions
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Intergroupe Francophone du Myelomelead
- Amgencollaborator
- Sanoficollaborator
- Bristol-Myers Squibbcollaborator
Study Sites (73)
Institut Jules Bordet
Brussels, 1070, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
Grand Hôpital de Charleroi - Site de Notre-Dame
Charleroi, B 6000, Belgium
Hôpital Jolimont
Haine-Saint-Paul, 7100, Belgium
CHU de Liège
Liège, 4000, Belgium
CHU UCL Namur (Site Godinne)
Yvoir, B 5530, Belgium
CHU Amiens Sud
Amiens, France
CHRU-Hôpital du Bocage
Angers, France
Centre Hospitalier d'Argenteuil Victor Dupouy
Argenteuil, France
Centre Hospitalier H.Duffaut
Avignon, France
Centre hospitalier de la Côte Basque
Bayonne, France
Hôpital Jean Minjoz
Besançon, France
Centre Hospitalier Simone Veil
Blois, France
Hôpital Avicenne
Bobigny, France
Polyclinique Bordeaux Nord Acquitaine
Bordeaux, France
CHRU Hôpital Haut Lévêque - Centre François Magendie
Bordeaux Pessac, France
Hôpital de Fleyriat
Bourg-en-Bresse, France
CHRU Brest - Hôpital A. Morvan
Brest, France
CHU Caen - Côte de Nacre
Caen, France
CH René Dubos
Cergy-Pontoise, France
Centre Hospitalier William Morey
Chalon-sur-Saône, 71100, France
CH Chambéry
Chambéry, France
Hôpital d'Instruction des Armées Percy
Clamart, France
Chu Estaing
Clermont-Ferrand, France
Centre Hospitalier Sud Francilien
Corbeil-Essonnes, France
CHU Henri Mondor
Créteil, France
CHU Dijon Hôpital d'enfants
Dijon, France
Centre Hospitalier Général
Dunkirk, France
CHRU Hôpital A. Michallon
Grenoble, France
CHD Vendée
La Roche-sur-Yon, France
CHV André Mignot - Université de Versailles
Le Chesnay, France
CH de Chartres - Hôpital Louis Pasteur
Le Coudray, France
Hôpital Jacques Monod
Le Havre, France
Centre Hospitalier
Le Mans, France
CHRU Hôpital Claude Huriez
Lille, France
GH de l'Institut Catholique Saint Vincent
Lille, France
Centre Hospitalier Universitaire (CHU) de Limoges
Limoges, France
Hôpital du Scorff
Lorient, France
Centre Léon Bérard
Lyon, France
Institut Paoli Calmettes
Marseille, France
CH Meaux
Meaux, France
Hôpital de Mercy (CHR Metz-Thionville)
Metz, France
Hopital Saint Eloi - CHU Montpellier
Montpellier, France
Hôpital E. Muller
Mulhouse, France
CHRU Hôtel Dieu
Nantes, France
Clinique de l'Archet
Nice, France
CHU Carémeau
Nîmes, France
CH La Source
Orléans, France
CHU Hôpital Saint Antoine
Paris, France
Hôpital Cochin
Paris, France
Hôpital Necker
Paris, France
Hôpital Saint Louis
Paris, France
Institut Curie
Paris, France
La Pitié- Salpetrière
Paris, France
CH Saint Jean
Perpignan, France
Centre Hospitalier de Perigueux
Périgueux, France
Hospices Civils de Lyon - Hôpital Lyon Sud
Pierre-Bénite Lyon, France
CHU Poitiers - Pôle régional de Cancérologie
Poitiers, France
Ch Annecy Genevois
Pringy, France
Centre Hospitalier Intercommunal de Cornouaille
Quimper, France
Hôpital Robert Debré
Reims, France
CHRU Hôpital de Pontchaillou
Rennes, France
Centre Henri Becquerel
Rouen, France
Centre Hospitalier Yves Le Foll
Saint-Brieuc, France
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, France
Centre Hospitalier de Saint-Quentin
Saint-Quentin, France
Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
Strasbourg, France
Pôle IUCT Oncopole CHU
Toulouse, France
CHRU Hôpital Bretonneau
Tours, France
CHRU Hôpitaux de Brabois
Vandœuvre-lès-Nancy, France
CHBA
Vannes, France
Gustave Roussy
Villejuif, France
CHU de La Réunion site Sud
Saint-Pierre, Reunion
Related Publications (3)
Perrot A, Lambert J, Hulin C, Pieragostini A, Karlin L, Arnulf B, Rey P, Garderet L, Macro M, Escoffre-Barbe M, Gay J, Chalopin T, Gounot R, Schiano JM, Mohty M, Leleu X, Manier S, Mariette C, Chaleteix C, Braun T, De Prijck B, Avet-Loiseau H, Mary JY, Corre J, Moreau P, Touzeau C; MIDAS Study Group. Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma. N Engl J Med. 2025 Jul 31;393(5):425-437. doi: 10.1056/NEJMoa2505133. Epub 2025 Jun 3.
PMID: 40459097DERIVEDPerrot A, Touzeau C, Lambert J, Hulin C, Caillot D, Karlin L, Arnulf B, Rey P, Garderet L, Macro M, Escoffre Barbe M, Gay J, Chalopin T, Gounot R, Schiano JM, Tiab M, Mohty M, Kuhnowski F, Fontan J, Manier S, Orsini-Piocelle F, Vincent L, Rigaudeau S, Leleu X, Hebraud B, Flet L, Malfuson JV, Jacquet C, Chaoui D, Meuleman N, Abarah W, Montes L, Benramdane R, Sonntag C, Zerazhi H, Danu A, Allangba O, Dib M, Roussel M, Cereja S, Depaus J, Branche N, Demarquette H, Richez V, Cherel B, Frenzel L, Vekemans MC, Bigot N, Avet-Loiseau H, Corre J, Moreau P. Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial. Blood. 2025 Jul 3;146(1):52-61. doi: 10.1182/blood.2024026230.
PMID: 39841461DERIVEDMohan M, Gundarlapalli S, Szabo A, Yarlagadda N, Kakadia S, Konda M, Jillella A, Fnu A, Ogunsesan Y, Yarlagadda L, Thalambedu N, Munawar H, Graziutti M, Al Hadidi S, Alapat D, Thanendrarajan S, Zangari M, van Rhee F, Schinke C. Tandem autologous stem cell transplantation in patients with persistent bone marrow minimal residual disease after first transplantation in multiple myeloma. Am J Hematol. 2022 Jun 1;97(6):E195-E198. doi: 10.1002/ajh.26530. Epub 2022 Mar 21. No abstract available.
PMID: 35285981DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Philippe Moreau, Professor
Nantes University Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 11, 2021
First Posted
June 22, 2021
Study Start
December 8, 2021
Primary Completion
September 30, 2024
Study Completion (Estimated)
September 30, 2028
Last Updated
November 7, 2024
Record last verified: 2024-11