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

Newly Diagnosed Multiple Myeloma Clinical Trial

— GEM21menos65  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05558319
• Other study ID #: GEM21menos65
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: October 2022
• Est. completion date: April 2029

Study information

• Verified date: September 2022
• Source: PETHEMA Foundation
• Contact: Carmen López-Carrero
• Phone: 0034 699 835 437
• Email: carmen[@]fundacionpethema.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III open-label, 3-arm, parallel, randomized, controlled trial. The allocation ratio 1:1:1 and outcome assessment are blind to group allocation. Patients will be randomized from 3 arms. Patients will receive VRD extended + ASCT plus ERI or Isatuximab-VRD + ASCT or Isatuximab-VID + ASCT.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 480
• Est. completion date: April 2029
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Newly Diagnosed Multiple Myeloma

Intervention

Drug:
• Bortezomib
Bortezomib
• Isatuximab
Isatuximab
• Iberdomide
Iberdomide
• Lenalidomide
Lenalidomide
• Dexamethasone
Dexamethasone

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Hospital Principe de Asturias	Alcalá de Henares	Madrid
Spain	Hospital Germans Trias i Pujol (ICO BADALONA)	Badalona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d´Hebron	Barcelona
Spain	ICO L´Hospitalet	Barcelona
Spain	Hospital Universitario de Cruces	Bilbao
Spain	Hospital Universitario de Burgos	Burgos
Spain	Complejo Hospitalario de Cáceres	Cáceres
Spain	Hospital Universitario de Cabueñes	Gijón
Spain	Hospital Universitari Dr. Josep Trueta (ICO Girona)	Girona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario de Guadalajara	Guadalajara
Spain	H.Universitario de Jerez de la Frontera	Jerez De La Frontera
Spain	Hospital Universitario de Canarias	La Laguna
Spain	Complejo Asistencial Universitario de León	León
Spain	Hospital Arnau de Vilanova (Lleida)	Lleida
Spain	Hospital San Pedro	Logroño
Spain	Complejo Hospitalario Lucus Augusti	Lugo
Spain	Fundación Jiménez Díaz-Ute	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital HLA Universitario Moncloa	Madrid
Spain	Hospital Universitario 12 de octubre	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario de Fuenlabrada	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Fundación Alcorcón	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario La Zarzuela	Madrid
Spain	Hospital Universitario Puerta del Hierro	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Costa del Sol	Málaga
Spain	Hospital Regional de Málaga	Málaga
Spain	Hospital U Niversitario Virgen de La Victoria	Málaga
Spain	Hospital Universitario Rey Juan Carlos	Móstoles
Spain	H. Morales Meseguer	Murcia
Spain	H. Un. Virgen de la Arrixaca	Murcia
Spain	Hospital General Universitario Santa Lucía	Murcia
Spain	Complejo Hospitalario Universitario de Ourense	Ourense
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Son Llatzer	Palma De Mallorca
Spain	Hospital Universitari Son Espases	Palma De Mallorca
Spain	Clinica Universidad Navarra (CUN)	Pamplona	Navarra
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Complejo Hospitalario de Pontevedra	Pontevedra
Spain	Hospital Universitario Quirón Salud Madrid	Pozuelo De Alarcón	Madrid
Spain	Hospital Clinico Universitario Salamanca	Salamanca
Spain	Hospital Universitario de Donostia	San Sebastián
Spain	Hospital Universitario Infanta Sofía	San Sebastián De Los Reyes
Spain	Complejo Hospitalario Universitario Nuestra Señora de la Candelaria	Santa Cruz De Tenerife
Spain	H. Universitario Marqués de Valdecilla	Santander
Spain	Complejo Hospitalario Santiago (CHUS)	Santiago De Compostela
Spain	Hospital General de Segovia	Segovia
Spain	Complejo Hospitalario Regional Virgen Del Rocío	Sevilla
Spain	H. Universitario de Valme	Sevilla
Spain	Hospital Universitario Reina Sofía	Sevilla
Spain	Hospital Universitari de Tarragona Joan XXIII	Tarragona
Spain	Hospital Universitari Mutua Terrassa	Terrassa
Spain	Complejo Hospitalario de Toledo (Virgen de la Salud)	Toledo
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic la Fe	Valencia
Spain	Hospital Universitario Dr. Peset Aleixandre	Valencia
Spain	H. U. Txagorritxu	Vitoria
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (5)

Lead Sponsor	Collaborator
PETHEMA Foundation	Adknoma, Bristol-Myers Squibb, Sanofi, Start from scratch

Country where clinical trial is conducted

Spain, 

References & Publications (36)

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Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Macé S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. doi: 10.1016/S0140-6736(19)32556-5. Epub 2019 Nov 14. Erratum in: Lancet. 2019 Dec 7;394(10214):2072. — View Citation

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Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. — View Citation

Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. — View Citation

Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. Epub 2006 Jul 20. Erratum in: Leukemia. 2006 Dec;20(12):2220. Leukemia. 2007 May;21(5):1134. — View Citation

Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017 Feb 4;389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X. Epub 2016 Dec 23. — View Citation

Fernández de Larrea C, Jiménez R, Rosiñol L, Giné E, Tovar N, Cibeira MT, Fernández-Avilés F, Martínez C, Rovira M, Bladé J. Pattern of relapse and progression after autologous SCT as upfront treatment for multiple myeloma. Bone Marrow Transplant. 2014 Feb;49(2):223-7. doi: 10.1038/bmt.2013.150. Epub 2013 Sep 30. — View Citation

Ferrero S, Ladetto M, Drandi D, Cavallo F, Genuardi E, Urbano M, Caltagirone S, Grasso M, Rossini F, Guglielmelli T, Cangialosi C, Liberati AM, Callea V, Carovita T, Crippa C, De Rosa L, Pisani F, Falcone AP, Pregno P, Oliva S, Terragna C, Musto P, Passera R, Boccadoro M, Palumbo A. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival. Leukemia. 2015 Mar;29(3):689-95. doi: 10.1038/leu.2014.219. Epub 2014 Jul 16. — View Citation

Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6. Review. — View Citation

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* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall Response Rate (ORR)	Percentage of participants with a confirmed partial response (PR) or better (PR, VGPR, CR, sCR).	Throughout the study. Approximately 78 months
Other	Complete Response Rate (CRR)	The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR)).	Throughout the study. Approximately 78 months
Other	Time to Response (TTR)	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
Other	Duration of Response (DoR)	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
Other	Overall Survival (OS)	Time from the start of treatment until the date of death due to any cause	Throughout the study. Approximately 78 months
Primary	Efficacy in terms of patients who are MRD-negative by NGF	Percentage of patients who are MRD-negative by next generation flow cytometry (NGF) after 18 cycles + ASCT comparing the efficacy of extended VRD + ASCT plus ERI & (Arm B) vs. IsatuximabVRD + ASCT (Arm A).	24 months
Secondary	Frequency of adverse events (AEs)	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.
Secondary	Progression-Free Survival (PFS)	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