Isa-Rd for Frail and/or Much Older Patients With Newly Diagnosed Multiple Myeloma

NCT05145400 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LCCC 1944
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

This research study is investigating the safety and effectiveness of using combination of isatuximab, lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma (MM). The study team will use lower doses than is currently standard for these drugs. Lower doses will be used to avoid or possibly reduce any unwanted side effects commonly associated with these drugs. Using lower doses of the combination isatuximab, lenalidomide and dexamethasone, has not been approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed MM.

Conditions

Multiple Myeloma; Cancer

Keywords

Multiple Myeloma; isatuximab; lenalidomide; Geriatric

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR, percentage of patients achieving a partial response or better per Revised Uniform Response Criteria by the International Myeloma Working Group (IMWG) criteria. Complete response (CR): Negative immunofixation of serum and urine, disappearance of soft tissue plasmacytomas, and \<5% plasma cells in bone marrow (BM). Stringent complete response (sCR): CR plus normal free light chains (FLC) ratio and absence of clonal plasma cells in BM biopsy. Very good partial response (VGPR):-Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M component plus urine M component \<100/24h. Partial response (PR) ≥50% reduction of serum M-protein \& reduction in 24-hour (24h) urinary M-protein by ≥90% or to \<200 mg/24h and if present at baseline, a ≥ 50% reduction in the size soft tissue plasmacytomas

  From Day 1 of study treatment up to 60 months

Secondary Outcomes (10)

• Treatment failure-free survival (TFFS) Time

  From Day 1 of study treatment up to 60 months

• Progression-Free Survival (PFS)

  From Day 1 of study treatment up to 60 months

• Maximum Depth of Response

  From Day 1 of study treatment up to 60 months

• Rate of achievement of bone marrow minimal residual disease (MRD) negativity

  From Day 1 of study treatment up to 60 months

• Clinical Benefit Rate (minimal response (MR) + ORR)

  From Day 1 of study treatment up to 60 months

Study Arms (1)

Single Arm

EXPERIMENTAL

All subjects will receive the same treatment on the study, consisting of isatuximab, lenalidomide, and dexamethasone with 28 days cycles.

Drug: Isatuximab; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Isatuximab DRUG

Pharmaceutical form: Solution for infusion Route of administration: Intravenous Isatuximab:10 mg/kg intravenous or 1400 mg subcutaneous (SC) via on-body delivery system (OBDS) will be administered in cycles 1-24.

Single Arm

Lenalidomide DRUG

Pharmaceutical form: Capsule for oral use, Route of administration: Oral Lenalidomide capsule will be given oral, the dose will be adjusted according to glomerular filtration rate (GFR): 15 mg daily if GFR \> 60 mL/min, 5 mg daily if GFR 30-60 mL/min, 2.5 mg daily if GFR \< 30 mL/min. Note that dialysis-dependence comprises an exclusion criterion for this study. Lenalidomide will be continued until disease progression, excessive toxicity or death.

Also known as: REVLIMID

Single Arm

Dexamethasone DRUG

Pharmaceutical form: Tablet for oral use, Route of administration: Oral Dexamethasone tablet will be given oral: 20 mg given on days 1, 8, 15 and 22 of cycles 1-8. Administration may continue beyond cycle 8, if needed, for the prevention of infusion reactions.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI). Consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator or protocol designee.
• Predicted high risk for severe toxicity from intensive induction regimens, such as standard (full-dose) Bortezomib, cyclophosphamide, dexamethasone (VCD), lenalidomide, bortezomib, and dexamethasone (RVD), or lenalidomide and weekly dexamethasone (Rd) as each regimen was published. (Such regimens often use, for example, twice-weekly bortezomib or lenalidomide at 25 mg.) High-risk is defined as one of the following:
• Score ≥ 2 (indicating "frail") on the International Myeloma Working Group instrument (IMWG; Palumbo et al. \[Blood 2015\]),
• Karnofsky Performance Status (KPS) ≤ 70,
• Felt not to be candidate for full-intensity induction by treating clinician due to comorbidities, performance status, or other factors not otherwise captured by the Palumbo system or performance status. The reason for the subject's non-candidacy for full-intensity therapy should be described in the clinical documentation.
• Subjects qualifying for enrollment by criterion C should be discussed with the Medical Monitor before enrollment, to ensure uniform application of this criterion across participating sites.
• Measurable MM diagnosed according to the following standard criteria. Criteria A and B must be met, in addition to C and/or D:
• Monoclonal plasma cells in bone marrow ≥ 10% and/or presence of biopsy-proven plasmacytoma
• Monoclonal protein (M-protein) present in serum and/or urine, defined as serum M-protein of ≥ 1 g/dL (0.5 g/dL for Immunoglobulin A (IgA) MM) OR urine M-protein of ≥ 200 mg/24 hours. Subjects lacking an M-protein meeting those criteria must have a serum free light chain assay with an involved light chain ≥ 10 mg/dL (100 mg/L) and an abnormal serum free light chain ratio.
• One or more MM-related organ dysfunction findings such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) criteria listed below:
• Calcium elevation in blood (serum calcium 1 mg/dL ≥ upper limit of normal or \> 11 mg/dL)
• Renal insufficiency (creatinine clearance \< 40 ml/min or serum creatinine \> 2 mg/dL)
• Anemia (hemoglobin \< 10 g/dL or ≥ 2 g/dL below normal)
• Bone lesions (lytic bone lesions) on x-rays, computerized tomography (CT), Magnetic resonance imaging (MRI) or Positron emission tomography (PET)

You may not qualify if:

• Active infection requiring systemic antibiotics or other serious infection within 14 days prior to study treatment.
• Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the subject or may interfere with compliance or interpretation of the study results.
• Light-chain (AL) amyloidosis. Subjects with secondary amyloidosis due to MM are eligible, if the amyloidosis is not felt to be a clinically significant issue (e.g., amyloid found incidentally on bone marrow core biopsy without evidence of amyloid-mediated organ compromise).
• Myocardial infarction within 3 months prior to study treatment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Hypersensitivity or history of 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 therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
• Known gastrointestinal (GI) disease that could interfere with the oral absorption or tolerance of dexamethasone or lenalidomide including difficulty swallowing.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patients with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational treatment should generally be eligible.
• Receiving other investigational agents less than 14 days or 5 half-lives of first dose of therapy on this protocol, whichever is longer.
• Concurrent use of other anti-cancer agents or treatments with possible exception of agents with low likelihood of affecting outcome of this study, such as adjuvant hormonal therapy for remote history of breast cancer.
• Known to be HIV+ or have active infection with hepatitis A, B, or C; or tuberculosis.
• Chronic daily corticosteroids for other, non-MM-related medical conditions exceeding low-dose (e.g., prednisone ≥ 10 mg daily or equivalent).
• Subject is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (5)

University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Novant Health New Hanover Regional Medical Center

Wilmington, North Carolina, 28401, United States

RECRUITING

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

isatuximab; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Sascha Tuchman, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shamina Williams

CONTACT

919-966-4432; Shamina_Williams@med.unc.edu

Lori Stravers

CONTACT

919-966-4432; Lori_Stravers@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 6, 2021
• Study Start: February 18, 2022
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2031
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)