Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

NCT05527340 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: GEM-IBERDARAX2021-002190-25
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 9

Brief Summary

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population. Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

Conditions

Multiple Myeloma

Keywords

De novo Multiple Myeloma; Transplant ineligible

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  The percentage of participants with a confirmed partial response (PR) or better (PR, Very good partial response (VGPR), Complete response (CR), stringent complete response (sCR)).Response rates will be monitored monthly, but the study will report the % of patients achieving CR rate at month 12, 18, 24 and yearly thereafter.

  Throught the study period. Approximately 6 years.

• Complete Response Rate (CRR)

  The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR).

  Throught the study period. Approximately 6 years.

Secondary Outcomes (12)

• Minimal Residual Disease (MRD) negativity rate

  Throught the study period. Approximately 6 years.

• Progression-Free Survival (PFS)

  Throught the study period. Approximately 6 years.

• Overall Survival (OS)

  Throught the study period. Approximately 6 years.

• Changes in the immune profiling.

  Throught the study period. Approximately 6 years.

• Health status/quality of life

  Baseline and throught the first 24 months.

Study Arms (2)

iberdomide + dexamethasone (IBERDEX)

EXPERIMENTAL

IBERDEX * Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO). * Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.

Drug: Iberdomide; Drug: Dexamethasone

iberdomide + daratumumab + dexamethasone (IBERDARADEX)

EXPERIMENTAL

IBERDARADEX * Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, PO. * Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO. * Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle Cycles will be of 4 weeks of duration (28 days).

Drug: Iberdomide; Drug: Dexamethasone; Drug: Daratumumab

Interventions

Iberdomide DRUG

Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO)

iberdomide + daratumumab + dexamethasone (IBERDARADEX); iberdomide + dexamethasone (IBERDEX)

Dexamethasone DRUG

Dexamethasone 40 mg (PO) (or 20 mg (PO) if patient ≥ 75 years old) should be administered on the days 1, 8, 15 and 22 of every 4-week cycle.

iberdomide + daratumumab + dexamethasone (IBERDARADEX); iberdomide + dexamethasone (IBERDEX)

Daratumumab DRUG

Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle Cycles will be of 4 weeks of duration (28 days).

iberdomide + daratumumab + dexamethasone (IBERDARADEX)

Eligibility Criteria

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

You may qualify if:

• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Patient must be able to understand the study procedures.
• Patient has given voluntary written informed consent before performance of any study-related procedure nor 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.
• Newly diagnosed multiple myeloma patient ≥65 years or younger but non-transplant eligible who requires start active treatment according to the IMWG published in 2014.
• 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/L (100 mg/dl), with an abnormal serum FLC ratio.
• Patient is defined as non-frail or frail using the modified-IMWG scale (APPENDIX 5). Frailty score according to the modified-IMWG scale will be collected before starting the treatment in order to ensure 30% of the patients are frail.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Patient must be ≥ 18 years of age
• Patient must have adequate organ function,
• Female childbearing potential patient (FCBP) criteria: 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 female of childbearing potential (FNCBP) OR
• Is a FCBP and
• She understands the potential teratogenic risk to the unborn child
• She understands the need for effective contraception, without interruption, 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions and for at least 3 months after the last dose of study treatment.

You may not qualify if:

• 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.
• Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma.
• Patient has invasive malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.
• 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 lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
• Pregnant or breastfeeding females.
• Patient is simultaneously enrolled in other interventional clinical trial.
• Received plasmapheresis within 7 days prior to the first dose of study drug.
• Patient has received prior radiotherapy 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. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to iberdomide or drugs chemically related to iberdomide, or any of the excipients contained in the formulation of the study treatment.
• Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to daratumumab or drugs chemically related to daratumumab, or any of the excipients contained in the formulation of the study treatment.
• Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to other monoclonal antibodies.
• Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to dexamethasone or drugs chemically related to dexamethasone, or any of the excipients contained in the formulation of the study treatment.
• Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
• Patient has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTC AE) Version 5.0.
• Patient evidence of cardiovascular risk including any of the following:

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Celgene-BMS: collaborator
• Janssen-Cilag, S.A.: collaborator
• LIDESEC: collaborator

Study Sites (9)

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

Clínica Universidad de Navarra

Pamplona, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario y Politécnico La Fe de Valencia

Valencia, Spain

Location

Related Publications (14)

• Mateos MV, San Miguel JF. Management of multiple myeloma in the newly diagnosed patient. Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):498-507. doi: 10.1182/asheducation-2017.1.498.

  PMID: 29222298 BACKGROUND

• Durie BGM, Kumar SK, Usmani SZ, Nonyane BAS, Ammann EM, Lam A, Kobos R, Maiese EM, Facon T. Daratumumab-lenalidomide-dexamethasone vs standard-of-care regimens: Efficacy in transplant-ineligible untreated myeloma. Am J Hematol. 2020 Dec;95(12):1486-1494. doi: 10.1002/ajh.25963. Epub 2020 Sep 5.

  PMID: 32804408 BACKGROUND

• Belotti A, Ribolla R, Cancelli V, Crippa C, Bianchetti N, Ferrari S, Bottelli C, Cattaneo C, Tucci A, De La Fuente Barrigon C, Rossi G. Transplant eligibility in elderly multiple myeloma patients: Prospective external validation of the international myeloma working group frailty score and comparison with clinical judgment and other comorbidity scores in unselected patients aged 65-75 years. Am J Hematol. 2020 Jul;95(7):759-765. doi: 10.1002/ajh.25797. Epub 2020 Apr 23.

  PMID: 32242970 BACKGROUND

• Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia. 2020 Jan;34(1):224-233. doi: 10.1038/s41375-019-0539-0. Epub 2019 Aug 19.

  PMID: 31427722 BACKGROUND

• Cruz-Jentoft AJ, Gonzalez B, de la Rubia J, Hernandez Rivas JA, Soler JA, Fernandez Lago C, Arnao M, Gironella M, Perez Persona E, Zudaire MT, Olivier C, Altes A, Garcia Guinon A, Nomdedeu B, Arnan M, Ramirez Payer A, Sanchez-Godoy P, Pajuelo N, Vilanova D, Monjil DF, Bonanad S; GAH Group. Further psychometric validation of the GAH scale: Responsiveness and effect size. J Geriatr Oncol. 2017 May;8(3):211-215. doi: 10.1016/j.jgo.2016.12.008. Epub 2016 Dec 22.

  PMID: 28017687 BACKGROUND

• 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. doi: 10.1056/NEJMoa1607751.

  PMID: 27705267 BACKGROUND

• Bahlis NJ, Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Krevvata M, Chiu C, Qin X, Okonkwo L, Trivedi S, Ukropec J, Qi M, San-Miguel J. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020 Jul;34(7):1875-1884. doi: 10.1038/s41375-020-0711-6. Epub 2020 Jan 30.

  PMID: 32001798 BACKGROUND

• Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Sutherland HJ, Lalancette M, Magen H, Iida S, Kim JS, Prince HM, Cochrane T, Oriol A, Bahlis NJ, Chari A, O'Rourke L, Wu K, Schecter JM, Casneuf T, Chiu C, Soong D, Sasser AK, Khokhar NZ, Avet-Loiseau H, Usmani SZ. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica. 2018 Dec;103(12):2088-2096. doi: 10.3324/haematol.2018.194282. Epub 2018 Sep 20.

  PMID: 30237262 BACKGROUND

• Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N, Basu S, Nahi H, Hulin C, Quach H, Goldschmidt H, O'Dwyer M, Perrot A, Venner CP, Weisel K, Mace JR, Raje N, Attal M, Tiab M, Macro M, Frenzel L, Leleu X, Ahmadi T, Chiu C, Wang J, Van Rampelbergh R, Uhlar CM, Kobos R, Qi M, Usmani SZ; MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019 May 30;380(22):2104-2115. doi: 10.1056/NEJMoa1817249.

  PMID: 31141632 BACKGROUND

• Perrot A, Facon T, Plesner T, Usmani SZ, Kumar S, Bahlis NJ, Hulin C, Orlowski RZ, Nahi H, Mollee P, Ramasamy K, Roussel M, Jaccard A, Delforge M, Karlin L, Arnulf B, Chari A, He J, Ho KF, Van Rampelbergh R, Uhlar CM, Wang J, Kobos R, Gries KS, Fastenau J, Weisel K. Health-Related Quality of Life in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Findings From the Phase III MAIA Trial. J Clin Oncol. 2021 Jan 20;39(3):227-237. doi: 10.1200/JCO.20.01370. Epub 2020 Dec 16.

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  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; Dexamethasone; daratumumab

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• María Victoria Mateos Manteca

  University of Salamanca

  STUDY CHAIR

• Verónica González de la Calle

  University of Salamanca

  STUDY CHAIR

• Jesús San Miguel Izquierdo

  Clínica Universidad de Navarra

  STUDY CHAIR

• Juan José Lahuerta Palacios

  Hospital Universitario 12 de Octubre

  STUDY CHAIR

• Joan Bladé Creixenti

  Hospital Clinic of Barcelona

  STUDY CHAIR

Central Study Contacts

Carmen López-Carrero

CONTACT

(+34) 699 835 437; carmen@fundacionpethema.es

Roberto Maldonado

CONTACT

(+34) 683 15 66 87; roberto.maldonado@fundacionpethema.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: September 2, 2022
• Study Start: September 1, 2022
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 2, 2022

Record last verified: 2022-09

Locations

ES (9)