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

NCT02514668

Description:

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).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: TED14154
  • SECONDARY ID: U1111-1163-1073
  • NCT ID: NCT02514668

Trial Conditions

  • Plasma Cell Myeloma

Trial Interventions

DrugSynonymsArms
IsatuximabSAR650984Isatuximab

Trial Purpose

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).

- 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 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.

Trial Arms

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

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 and at least 6 weeks from the last treatment of 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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Dose Limiting Toxicities (DLTs)
Time Frame:Up to 4 weeks
Safety Issue:Yes
Description:

Secondary Outcome Measures

Measure:Assessment of PK parameters: partial area under the serum concentration time curve (AUC)
Time Frame:1 week after first treatment
Safety Issue:No
Description:
Measure:Assessment of PK parameters: maximum observed concentration (Cmax)
Time Frame:1 week after first treatment
Safety Issue:No
Description:
Measure:Part B: Number of patients with adverse events and changes laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling
Time Frame: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
Safety Issue:Yes
Description:
Measure:Part B: Duration of Response (DOR)
Time Frame:Up to 12 months from the last patient in
Safety Issue:No
Description:
Measure:Part B: Clinical Benefit Rate(CDR)
Time Frame:Up to 12 months from the last patient in
Safety Issue:No
Description:
Measure:Part B: Progression Free Survival
Time Frame:Up to 12 months from the last patient in
Safety Issue:No
Description:
Measure:Part B: Levels of isatuximab antibodies
Time Frame:Up to 12 months after the last treatment
Safety Issue:No
Description:

Trial Keywords