Isatuximab, Pomalidomide, Elotuzumab and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

NCT04835129 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRO00041365
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multicenter, open-label phase II study in subjects with relapsed and/or refractory multiple myeloma with at least two prior lines of therapy. The main study consists of three phases: a 28-day screening phase, treatment phase that consists of 28-day cycles of isatuximab with elotuzumab, pomalidomide, and dexamethasone and a follow-up phase.

Conditions

Multiple Myeloma

Keywords

relapsed and/or refractory multiple myeloma; salvage therapy

Outcome Measures

Primary Outcomes (1)

• The number of subjects in each status category of the International Myeloma Working Group (stringent complete response, complete response, very good partial response, partial response).

  This will be measured using the International Myeloma Working Group criteria.

  1 month until last patient progressed

Study Arms (2)

Safety Run-in

EXPERIMENTAL

Six subjects will be enrolled. Isatuximab (10 mg/kg) intravenous (IV) on days 2, 8, 15, 22 of cycle 2 and days 1 and 15 of subsequent cycles. Pomalidomide (4 mg) by mouth (PO) days 1-21 of each cycle. Elotuzumab (10 mg/kg) on days 1, 8, 15, 22 of cycles 1 and 2; 20 mg/kg on day 1 of subsequent cycles. Dexamethasone 40 mg (20 mg if \>75 years) PO or IV on days 1, 8,15 and 22 of each cycle.

Drug: Isatuximab (for run-in portion); Drug: Pomalidomide; Drug: Elotuzumab; Drug: Dexamethasone

Expansion

EXPERIMENTAL

Subjects with relapsed and/or refractory multiple myeloma will be enrolled. Isatuximab (10 mg/kg) IV on days 2, 8, 15, 22 of cycle 1 and days 1 and 15 of subsequent cycles. Pomalidomide (4 mg) PO days 1-21 of each cycle. Elotuzumab (10 mg/kg) on days 1, 8, 15, 22 of cycles 1 and 2; 20 mg/kg on day 1 of subsequent cycles. Dexamethasone 40 mg (20 mg if \>75 years) PO or IV on days 1, 8,15 and 22 of each cycle.

Drug: Isatuximab (for expansion); Drug: Pomalidomide; Drug: Elotuzumab; Drug: Dexamethasone

Interventions

Isatuximab (for run-in portion) DRUG

10 mg/kg IV on days 2, 8, 15, 22 of cycle 2 and days 1 and 15 of subsequent cycles.

Also known as: Sarclisa, SAR-650984, isatuximab-irfc

Safety Run-in

Isatuximab (for expansion) DRUG

10 mg/kg IV on days 2, 8, 15, 22 of cycle 1 and days 1 and 15 of subsequent cycles.

Also known as: Sarclisa, SAR-650984, isatuximab-irfc

Expansion

Pomalidomide DRUG

4 mg PO days 1-21 of each cycle.

Also known as: Pomalyst, Imnovid

Expansion; Safety Run-in

Elotuzumab DRUG

10 mg/kg on days 1, 8, 15, 22 of cycles 1 and 2; 20 mg/kg on day 1 of subsequent cycles.

Also known as: Empliciti, HuLuc63

Expansion; Safety Run-in

Dexamethasone DRUG

40 mg (20 mg if \>75 years) PO or IV on days 1, 8,15 and 22 of each cycle.

Also known as: Baycadron, Decadron, DexPak, TaperDex, Zema-Pak, ZoDex, Zonacort

Expansion; Safety Run-in

Eligibility Criteria

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

You may qualify if:

• Voluntary consent must be given before performance of any study related procedure.
• Male or female subjects ≥18 years.
• Multiple myeloma subjects with at least 2 prior therapies that included lenalidomide and proteasome inhibitor combined or in different regimens, and refractory to most recent line of therapy.
• Measurable disease as defined by any of the following:
• Serum M-protein level ≥0.5 g/dL OR
• Urine M-protein level ≥200 mg/24 hours; OR
• Light chain multiple myeloma without measurable disease in the urine: serum Ig free light chains (FLC) ≥10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Female subjects who:
• Are postmenopausal (see Appendix 4 for definition) for at least one year before the screening visit, OR
• Are surgically sterile, OR
• Females of childbearing potential or male subjects with female partners of childbearing potential shall be required to use effective contraceptive methods (double barrier method, intrauterine device, oral contraception or abstinence) starting two weeks before first study drug(s) administration, while on therapy and for 16 weeks following the last dose of study drug(s). A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Any of the following highly effective methods of contraception are accepted:
• Established use of oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation.
• Established use of oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation.
• Placement of an intrauterine device or intrauterine hormone-releasing system.

You may not qualify if:

• Diagnosed or treated for malignancy other than multiple myeloma, except:
• Malignancy treated with curative intent and with no known active disease present for ≥3 years before enrollment.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ (e.g., cervical, breast) with no evidence of disease.
• Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma.
• Subjects refractory to prior signaling lymphocytic activation molecule F7 (SLAMF7) monoclonal antibody
• Prior cluster of differentiation 38 (CD38) monoclonal antibody is allowed as long it has been \>6 months and patients had achieved at least a partial response or better.
• Subject refractory or intolerant to prior pomalidomide therapy.
• Known chronic obstructive pulmonary disease
• Known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification. Note: Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study.
• Known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have untreated or active hepatitis C.
• Concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
• Clinically significant cardiac disease, including:
• Myocardial infarction within six months before enrollment or 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 higher) or clinically significant electrocardiogram (ECG) abnormalities.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (2)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade 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.

  PMID: 27511158 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; pomalidomide; elotuzumab; Dexamethasone; Calcium Dobesilate

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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Binod Dhakal, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: April 8, 2021
• Study Start: January 10, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)