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

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02514668
• Collaborator: (none)
• Enrollment: 55
• Locations: 18
• Arm: 1
• Actual Duration (Months): 75
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Plasma Cell Myeloma	Drug: Isatuximab	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Dose-escalation and Multi-center Study to Evaluate the Safety, Pharmacokinetics and Efficacy of SAR650984 (Isatuximab) in Patients With Relapsed/Refractory Multiple Myeloma
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Dec 2, 2021
• Actual Study Completion Date: Dec 2, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Isatuximab 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; Pharmaceutical form: solution for infusion Route of administration: intravenous; Other Names: SAR650984 Sarclisa

Outcome Measures

Primary Outcome Measures

1. Part A: Dose Limiting Toxicities (DLTs) [Up to 4 weeks]

2. 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]

3. Part B: Overall Response Rate (ORR) [4 months]

Secondary Outcome Measures

1. Assessment of PK parameters: partial area under the serum concentration time curve (AUC) [1 week after first treatment]

2. Assessment of PK parameters: maximum observed concentration (Cmax) [1 week after first treatment]

3. 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]

4. Part B: Duration of Response (DOR) [Up to 12 months from the last patient in]

5. Part B: Clinical Benefit Rate (CBR) [Up to 12 months from the last patient in]

6. Part B: Progression Free Survival (PFS) [Up to 12 months from the last patient in]

7. Part B: Levels of isatuximab antibodies [Up to 12 months from the last patient in]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 840003	Scottsdale	Arizona	United States	85054
2	Investigational Site Number 840004	San Francisco	California	United States	94117
3	Investigational Site Number 840011	Detroit	Michigan	United States	48201
4	Investigational Site Number 840015	Saint Louis	Missouri	United States	63110
5	Investigational Site Number 840005	Hackensack	New Jersey	United States	07601
6	Investigational Site Number 840010	Durham	North Carolina	United States	27707
7	Investigational Site Number 840013	Canton	Ohio	United States	44718
8	Investigational Site Number 840001	Nashville	Tennessee	United States	37232
9	Investigational Site Number 840002	Salt Lake City	Utah	United States	84112-5550
10	Investigational Site Number 840006	Milwaukee	Wisconsin	United States	53226
11	Investigational Site Number 203002	Brno		Czechia	62500
12	Investigational Site Number 203001	Praha 2		Czechia	12808
13	Investigational Site Number 250008	Creteil Cedex		France	94010
14	Investigational Site Number 250005	Montpellier Cedex 5		France	34295
15	Investigational Site Number 250002	Nantes Cedex 01		France	44093
16	Investigational Site Number 250004	Pessac		France	33600
17	Investigational Site Number 250001	Poitiers		France	86021
18	Investigational Site Number 250006	Vandoeuvre-Les-Nancy Cedex		France	54511

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02514668
• Other Study ID Numbers: TED14154; U1111-1163-1073
• First Posted: Aug 4, 2015
• Last Update Posted: Apr 25, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sanofi: Anti-CD38 monoclonal antibody
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

No Results Posted as of Apr 25, 2022