Clinical Trials /

Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT04045795

Description:

Primary Objectives: - To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV) - To evaluate the pharmacokinetics (PK) of SC and IV isatuximab Secondary Objectives: - To estimate absolute bioavailability of SC and IV isatuximab - To measure receptor occupancy (RO) after isatuximab SC versus IV administration - To assess efficacy of isatuximab after SC and IV administration - To assess patient expectations prior to and patient experience and satisfaction after SC administration - To evaluate potential immunogenicity of SC or IV isatuximab

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
  • Official Title: A Multi-center, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Efficacy of Subcutaneous and Intravenous Isatuximab (SAR650984) in Combination With Pomalidomide and Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

Clinical Trial IDs

  • ORG STUDY ID: TCD15484
  • SECONDARY ID: 2018‐001996‐19
  • SECONDARY ID: U1111-1211-9525
  • NCT ID: NCT04045795

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
isatuximab SAR650984Dose regimen 1
pomalidomideDose regimen 1
dexamethasoneDose regimen 1

Purpose

Primary Objectives: - To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV) - To evaluate the pharmacokinetics (PK) of SC and IV isatuximab Secondary Objectives: - To estimate absolute bioavailability of SC and IV isatuximab - To measure receptor occupancy (RO) after isatuximab SC versus IV administration - To assess efficacy of isatuximab after SC and IV administration - To assess patient expectations prior to and patient experience and satisfaction after SC administration - To evaluate potential immunogenicity of SC or IV isatuximab

Detailed Description

      Total study duration is variable depending on treatment and follow-up periods, including 21
      days of screening, and treatment period until disease progression, unacceptable adverse
      reaction or other reason for discontinuation. End of treatment will be 30 days after last
      administration of investigational medicinal product, or approximately 14 months after first
      study treatment administration.
    

Trial Arms

NameTypeDescriptionInterventions
Dose regimen 1ExperimentalIsatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
  • isatuximab SAR650984
  • pomalidomide
  • dexamethasone
Dose regimen 2ExperimentalIsatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
  • isatuximab SAR650984
  • pomalidomide
  • dexamethasone
Dose regimen 3ExperimentalIsatuximab SC administration dose level 3 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
  • isatuximab SAR650984
  • pomalidomide
  • dexamethasone
Dose regimen 4ExperimentalIsatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
  • isatuximab SAR650984
  • pomalidomide
  • dexamethasone
Dose regimen 5ExperimentalIsatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle
  • isatuximab SAR650984
  • pomalidomide
  • dexamethasone

Eligibility Criteria

        Inclusion criteria:

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in the
             protocol.

          -  Participant must be above 18 years of age inclusive, at the time of signing the
             informed consent.

          -  Participant has been previously diagnosed with multiple myeloma (MM) based on standard
             criteria and currently requires treatment because MM has relapsed following a
             response, according to International Myeloma Working Group (IMWG) criteria.

          -  Participant has received at least two previous therapies including lenalidomide and a
             proteasome inhibitor and has demonstrated disease progression on last therapy or after
             completion of the last therapy.

          -  Participants with measurable disease defined as at least one of the following:

          -  Serum M protein ≥ 0.5 g/dL (≥5 g/L).

          -  Urine M protein ≥ 200 mg/24 hours.

          -  Serum free light chain (FLC) assay: Involved FLC assay ≥ 10 mg/dL (≥ 100 mg/L) and an
             abnormal serum FLC ratio (<0.26 or >1.65).

          -  Male or female: Contraceptive use by men or women.

        Exclusion criteria:

          -  Malignancy within 3 years prior to enrollment.

          -  Eastern Cooperative Oncology Group (ECOG) performance status score >2.

          -  Inadequate hematological, liver or renal function.

          -  Serum calcium (corrected for albumin) level above the upper limit of normal (ULN)
             range.

          -  Primary refractory or intolerant to prior therapy with any anti-CD38 mAb or had
             disease progression during anti-CD38 mAb, administered as last therapy.

          -  Participant did not achieve a minimal response or better to at least one of the
             previous lines of treatment (ie, primary refractory disease is not eligible).

          -  Received any investigational drug within 14 days or 5 half-lives of the
             investigational drug, whichever is longer.

          -  Prior anti-cancer therapy within 14 days.

          -  Any >Grade 1 adverse reaction unresolved from previous treatments according to the
             NCI-CTCAE v5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without
             pain is allowed.

          -  Previous allogeneic stem cell transplantation with active Graft Versus Host Disease or
             being under immunosuppressive therapy in the last 2 months previously to the inclusion
             in the trial.

          -  Daily requirement for corticosteroids.

          -  Known to be HIV+ or to have hepatitis A, B or C active infection.

          -  Active tuberculosis and severe infections requiring treatment with antibiotic
             parenteral administration.

          -  Any clinically significant, uncontrolled medical conditions that, in the
             Investigator's opinion, would expose excessive risk to the patient or may interfere
             with compliance or interpretation of the study results.

          -  History of erythema multiforme or severe hypersensitivity to prior immunomodulatory
             drugs (IMiDs).

          -  Hypersensitivity or history of intolerance to immunomodulatory drugs (IMiDs),
             dexamethasone, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as
             base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of
             the other components of study therapy that are not amenable to premedication with
             steroids and histamine H2 blockers or would prohibit further treatment with these
             agents.

          -  Inability to tolerate thromboprophylaxis.

        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:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of adverse events (AEs)
Time Frame:Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Number of participants with adverse events

Secondary Outcome Measures

Measure:Estimation of absolute bioavailability of isatuximab
Time Frame:Day 8
Safety Issue:
Description:Absolute bioavailability of isatuximab SC, expressed as a percentage, estimated from AUC0-168h obtained after intravenous (IV) and extravascular (EV) administration
Measure:Overall response rate (ORR)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:ORR is the proportion of patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) using the IMWG response criteria
Measure:Duration of response (DOR)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Time from the date of the first response to the date of first progressive disease (PD) or death, whichever happens first
Measure:Time to response (TTR)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Time from the date of first study treatment to the first response
Measure:Time to progression (TTP)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Time from date of first study treatment to date of first documentation of progressive disease
Measure:Overall survival (OS)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Time from the date of first study treatment to date of death from any cause
Measure:Clinical benefit rate (CBR)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Proportion of patients with sCR, CR, VGPR, PR or minimal response (MR) according to IMWG criteria
Measure:Progression free survival (PFS)
Time Frame:From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Time from date of first study treatment to date of first documentation of progressive disease or death
Measure:Comparison of patient expectations and satisfaction: Patient Expectations and Satisfaction Questionnaires
Time Frame:Cycles 1 and 2 (28 days per Cycle), and 30 days after last isatuximab administration (up to approximately 14 months after first study treatment administration)
Safety Issue:
Description:Comparison of patient expectations and satisfaction will be assessed using Patient Expectations and Satisfaction Questionnaires before and after subcutaneous (SC) administration, where a score of 1 = not satisfied and a score of 5 = extremely satisfied
Measure:Immunogenicity: Anti drug antibody levels
Time Frame:Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)
Safety Issue:
Description:Incidence of patients with anti drug antibodies against isatuximab
Measure:Biomarker: Change in CD38 receptor occupancy
Time Frame:At screening and at Day 1 of Cycle 2 (28 days per Cycle) (predose); to be stopped once the isatuximab SC dose has been selected.
Safety Issue:
Description:Change in CD38 receptor occupancy from baseline

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

February 3, 2020