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

NCT ID: NCT02514668

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-01
• Study Completion Date: 2021-12-02

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).

Detailed Description

Study duration for an individual patient will include a screening period for inclusion of up to 3 weeks, the treatment period and, a follow up period. Treatment with SAR650984 (isatuximab) may continue until disease progression, unacceptable adverse event, or other reason for discontinuation.

After study treatment discontinuation, an end of treatment visit will be done at 30 days to assess safety and PK, and at 30 and 60 days for anti-drug antibody (ADA). If the ADA is positive at Day 60, ADA will be repeated every 30 days until ADA is negative.

Patients with partial remission or better who discontinue treatment for reasons other than progression of disease will be followed monthly until progression or initiation of subsequent therapy, the final analysis cutoff date, whichever comes first.

Conditions

Plasma Cell Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Isatuximab

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

Group Type: EXPERIMENTAL

Isatuximab

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Interventions

Isatuximab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

SAR650984; Sarclisa

Eligibility Criteria

Inclusion Criteria

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.
• Signed written informed consent and be willing and able to complete all study-related procedures.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840003

Scottsdale, Arizona, United States

Investigational Site Number 840004

San Francisco, California, United States

Investigational Site Number 840011

Detroit, Michigan, United States

Investigational Site Number 840015

St Louis, Missouri, United States

Investigational Site Number 840005

Hackensack, New Jersey, United States

Investigational Site Number 840010

Durham, North Carolina, United States

Investigational Site Number 840013

Canton, Ohio, United States

Investigational Site Number 840001

Nashville, Tennessee, United States

Investigational Site Number 840002

Salt Lake City, Utah, United States

Investigational Site Number 840006

Milwaukee, Wisconsin, United States

Investigational Site Number 203002

Brno, , Czechia

Investigational Site Number 203001

Prague, , Czechia

Investigational Site Number 250008

Créteil, , France

Investigational Site Number 250005

Montpellier, , France

Investigational Site Number 250002

Nantes, , France

Investigational Site Number 250004

Pessac, , France

Investigational Site Number 250001

Poitiers, , France

Investigational Site Number 250006

Vandœuvre-lès-Nancy, , France

Countries

United States; Czechia; France

References

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.

Reference Type: DERIVED

PMID: 33980831 (View on PubMed)

Other Identifiers

U1111-1163-1073

Identifier Type: OTHER

Identifier Source: secondary_id

TED14154

Identifier Type: -

Identifier Source: org_study_id