Multicenter Phase 2 Study of Subcutaneous Isatuximab Plus Bortezomib, Lenalidomide and Dexamethasone in the Treatment of Newly Diagnosed Transplant Ineligible Multiple Myeloma

NCT05889221 | Active Not Recruiting DMC

• 1 other identifier: ISASOCUT - IFM2022-05
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Isatuximab was developed on a sub-cutaneous (SC) administration format. SC administration is expected to be more convenient for the patient, with a much shorter duration of administration compared to the currently approved IV route. The SC Isatuximab RP2D fixed dose was determined at 1400 mg in a phase1b assessing SC Isatuximab in combination with pomalidomide and dexamethasone in RRMM patients. A similar activity and a favorable safety administration profile compared to the IV formulation, was shown in this trial, as expected (Moreau et al, ASH 2021; Quach et al, ASCO 2022). This data should be confirmed in the ongoing IRAKLIA/EFC15951 phase 3 study, that compared in the RRMM, isatuximab plus pomalidomide and dexamethasone IV versus SC. Whether isatuximab SC, fixed 1400 mg dose, will show similar efficacy and safety profile as to anti-CD38Rd+V remains to be demonstrated. The investigators have planned to study the combination of SC isatuximab plus VRd (IsVRd) in patients with NDMM NTE in a phase 2 study across IFM (Intergroupe Francophone du Myeloma) centers in France to compare indirectly this data to the data obtained from studies that have studied this association in that population with the IV isatuximab formulation.

Conditions

Multiple Myeloma; Myeloma Multiple; Myeloma

Keywords

ISATUXIMAB; ISASOCUT; Bortezomib; Lenalidomide; Dexamethasone; VGPR

Outcome Measures

Primary Outcomes (1)

• VGPR Rate

  The primary outcome is the VGPR rate or better (as best response) using IMWG criteria.

  The primary outcoume will be evaluate up to 8 months after the treatment after treatment has begun.

Study Arms (1)

Combination isatuximab SC, lenalidomide, bortezomib and dexamethasone

EXPERIMENTAL

Other: Drug and medical device

Interventions

Drug and medical device OTHER

Isatuximab will be administered in the hospital by an healthcare professional in the periumbilical region at a single site, using an investigational device injector; injection site will be rotated from one administration to the other.

Combination isatuximab SC, lenalidomide, bortezomib and dexamethasone

Eligibility Criteria

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

You may qualify if:

• Must be able to understand and voluntarily sign an informed consent form
• Must be able to adhere to the study visit schedule and other protocol requirements
• Patient able to swallow the various oral treatments
• Life expectancy \> 6 months
• Subject, male or female, must be at least ≥ 65 years of age
• Must have a Newly diagnosed Multiple Myeloma requiring therapy (SLiM CRAB criteria) (see appendix 18.2) 6.1. Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma 6.2. Revised International Myeloma Working Group diagnostic criteria for multiple myeloma
• Myeloma defining events:
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: • Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \>2.75 mmol/L (\>11 mg/dL) • Renal insufficiency: creatinine clearance ≤40 mL per min† or serum creatinine ≥177 μmol/L (≥2 mg/dL)
• †Measured or estimated by validated equations
• Anemia: hemoglobin value of ≥ 20 g/L below the lower limit of normal, or hemoglobin value ≤100 g/L
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT ‡
• If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage\* ≥60%
• Involved/uninvolved serum free light chain ratio ≥100

You may not qualify if:

• Subject has a diagnosis of primary systemic amyloidosis, monoclonal gammopathy of undetermined significance, or smouldering multiple myeloma.
• Subject has a diagnosis of Waldenström's disease, 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 prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
• Subject has had radiation therapy within 7 days study treatment\*
• \* unless done for antalgic reason or in case of functional risk for the patient.
• Subject has had plasmapheresis within 7 days study treatment \*
• Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
• Known to be seropositive for history of human immunodeficiency virus (HIV).
• Known to have hepatitis B active or uncontrolled infection (positive HBsAg and/or HBV DNA)
• Known to have hepatitis C active infection (positive HCV RNA and negative anti-HCV)
• Subject has any clinically significant medical or psychiatric condition or disease (e.g., uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) in the investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results.
• Subject has active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics.
• Subject has clinically significant cardiac disease, including:
• myocardial infarction within 6 months before study treatment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
• uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 5 Grade ≥2) or clinically significant ECG abnormalities or LVEF \< 40 % 14. Subject has known allergies, hypersensitivity, or intolerance to steroids, mannitol, pregelatinized starch, sodium 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, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure).

Sponsors & Collaborators

• Sanofi: collaborator
• Intergroupe Francophone du Myelome: collaborator
• Poitiers University Hospital: lead

Study Sites (1)

CHU Poitiers

Poitiers, 86000, France

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Pharmaceutical Preparations; Equipment and Supplies

Condition Hierarchy (Ancestors)

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

Study Officials

• BOBIN Arthur, Dr

  Poitiers University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2023
• First Posted: June 5, 2023
• Study Start: October 23, 2023
• Primary Completion: March 16, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

FR (1)