A Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Isatuximab in Patients With Multiple Myeloma

NCT02514668 | Completed Phase 1

• 2 other identifiers: TED14154U1111-1163-1073
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 18

Brief Summary

Primary Objective:

• Part A: To evaluate the safety of SAR650984 (isatuximab) in patients with relapsed/refractory multiple myeloma (RRMM).
• Part B: To evaluate the activity of SAR650984 (isatuximab) as assessed by overall response rate (ORR) in RRMM patients previously treated with daratumumab. Secondary Objectives:
• Part A:
• To determine the pharmacokinetics (PK) of SAR650984 (isatuximab) in patients with RRMM.
• Part B:
• To evaluate the safety of SAR650984 (isatuximab).
• To evaluate the efficacy of SAR650984 (isatuximab) as assessed by duration of response (DOR), clinical benefit rate (CBR) and progression free survival (PFS).
• To assess the pharmacokinetics (PK) of SAR650984 (isatuximab) and daratumumab at baseline.
• To evaluate the immunogenicity of SAR650984 (isatuximab).

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (3)

• Part A: Dose Limiting Toxicities (DLTs)

  Up to 4 weeks

• Part A: Number of patients with adverse events (AEs) and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling

  Up to 30 days following the last administration of study treatment or up to 12 months for ongoing related AE, ongoing serious AE and new related AE

• Part B: Overall Response Rate (ORR)

  4 months

Secondary Outcomes (7)

• Assessment of PK parameters: partial area under the serum concentration time curve (AUC)

  1 week after first treatment

• Assessment of PK parameters: maximum observed concentration (Cmax)

  1 week after first treatment

• Part B: Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling

  Up to 30 days following the last administration of study treatment or up to 12 months for ongoing related AE, ongoing serious AE and new related AE

• Part B: Duration of Response (DOR)

  Up to 12 months from the last patient in

• Part B: Clinical Benefit Rate (CBR)

  Up to 12 months from the last patient in

Study Arms (1)

Isatuximab

EXPERIMENTAL

Isatuximab (escalating dose) on Days 1, 8, 15, and 22, then Days 1 and 15 in 28-day cycles up to disease progression

Drug: Isatuximab

Interventions

Isatuximab DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: SAR650984, Sarclisa

Isatuximab

Eligibility Criteria

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

You may qualify if:

• Part A
• Patients must have a known diagnosis of multiple myeloma (MM) with evidence of measurable disease, as defined below, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria:
• Serum M-protein ≥1g/dL, or urine M-protein ≥200 mg/24 hours, OR
• In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Patients must have received at least 3 prior lines of therapy for MM and must include treatment with an immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (for ≥2 cycles or ≥2 months of treatment). Induction therapy and stem cell transplant (± maintenance) will be considered as one regimen within a line, OR
• Patients whose disease is double refractory to an IMiD and a proteasome inhibitor. For patients who have received more than one type of IMiD and proteasome inhibitor, their disease must be refractory to the most recent one.
• Patients must have achieved a minimal response (MR) or better to at least one prior line of therapy.
• Patients must have received an alkylating agent (for ≥2 cycles or ≥2 months of treatment) either alone or in combination with other MM treatments (history of stem cell transplant is acceptable). Treatment with high-dose Melphalan for stem cell transplantation meets this requirement.
• Signed written informed consent and be willing and able to complete all study-related procedures.
• Part B
• Patients must have a known diagnosis of multiple myeloma (MM) with evidence of measurable disease, as defined below, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria:
• Serum M-protein ≥1g/dL, or urine M-protein ≥200 mg/24 hours, OR
• In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio.
• Patients must have received at least 3 cycles of daratumumab treatment with at least 6 weeks from the last treatment with daratumumab to the first study treatment OR at least 2 cycles of daratumumab treatment in case another therapy is given between daratumumab and isatuximab with at least 12 weeks from the last treatment with daratumumab to the first study treatment.
• Patients must have achieved MR or better to at least 1 prior line of therapy.

You may not qualify if:

• Patients \<18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status \>2.
• Poor bone marrow reserve.
• Poor organ function.
• Known intolerance/hypersensitivity to IMiDs, dexamethasone, boron or mannitol, sucrose, histidine, or polysorbate 80.
• Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or comorbid condition, which, in the opinion of the Investigator, could interfere with the safety, the compliance with the study, or with the interpretation of the results.
• Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (18)

Investigational Site Number 840003

Scottsdale, Arizona, 85054, United States

Location

Investigational Site Number 840004

San Francisco, California, 94117, United States

Location

Investigational Site Number 840011

Detroit, Michigan, 48201, United States

Location

Investigational Site Number 840015

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840005

Hackensack, New Jersey, 07601, United States

Location

Investigational Site Number 840010

Durham, North Carolina, 27707, United States

Location

Investigational Site Number 840013

Canton, Ohio, 44718, United States

Location

Investigational Site Number 840001

Nashville, Tennessee, 37232, United States

Location

Investigational Site Number 840002

Salt Lake City, Utah, 84112-5550, United States

Location

Investigational Site Number 840006

Milwaukee, Wisconsin, 53226, United States

Location

Investigational Site Number 203002

Brno, 62500, Czechia

Location

Investigational Site Number 203001

Prague, 12808, Czechia

Location

Investigational Site Number 250008

Créteil, 94010, France

Location

Investigational Site Number 250005

Montpellier, 34295, France

Location

Investigational Site Number 250002

Nantes, 44093, France

Location

Investigational Site Number 250004

Pessac, 33600, France

Location

Investigational Site Number 250001

Poitiers, 86021, France

Location

Investigational Site Number 250006

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (1)

• Mikhael J, Belhadj-Merzoug K, Hulin C, Vincent L, Moreau P, Gasparetto C, Pour L, Spicka I, Vij R, Zonder J, Atanackovic D, Gabrail N, Martin TG, Perrot A, Bensfia S, Weng Q, Brillac C, Semiond D, Mace S, Corzo KP, Leleu X. A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab. Blood Cancer J. 2021 May 12;11(5):89. doi: 10.1038/s41408-021-00478-4. No abstract available.

  PMID: 33980831 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2015
• First Posted: August 4, 2015
• Study Start: September 1, 2015
• Primary Completion: December 2, 2021
• Study Completion: December 2, 2021
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

CZ (2); US (10); FR (6)