Clinical Trials /

A Study of Isatuximab-based Therapy in Participants With Lymphoma

NCT03769181

Description:

Primary Objectives: Phase 1 -To characterize the safety and tolerability of isatuximab in combination with cemiplimab in participants with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL), and to confirm the recommended Phase 2 dose (RP2D). Phase 2 - Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naïve cHL): To assess the complete remission (CR) rate of isatuximab in combination with cemiplimab. - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To assess the objective response rate (ORR) of isatuximab in combination with cemiplimab. Secondary Objectives: - To evaluate the safety of the RP2D of the combination of isatuximab with cemiplimab. - To evaluate the safety of the combination of isatuximab with cemiplimab and radiotherapy in patients with cHL. - To evaluate the immunogenicity of isatuximab and cemiplimab when given in combination. - To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab when given in combination. - To assess overall efficacy of isatuximab in combination with cemiplimab and isatuximab in combination with cemiplimab and radiotherapy.

Related Conditions:
  • Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Isatuximab-based Therapy in Participants With Lymphoma
  • Official Title: A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab in Combination With Other Anti-cancer Therapies in Participants With Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: ACT15320
  • SECONDARY ID: 2018‐002442‐37
  • SECONDARY ID: U1111-1211-9010
  • NCT ID: NCT03769181

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
isatuximab SAR650984Phase 1: cHl/DLBCL/PTCL
cemiplimab REGN2810Phase 1: cHl/DLBCL/PTCL

Purpose

Primary Objectives: Phase 1 -To characterize the safety and tolerability of isatuximab in combination with cemiplimab in participants with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL), and to confirm the recommended Phase 2 dose (RP2D). Phase 2 - Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naïve cHL): To assess the complete remission (CR) rate of isatuximab in combination with cemiplimab. - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To assess the objective response rate (ORR) of isatuximab in combination with cemiplimab. Secondary Objectives: - To evaluate the safety of the RP2D of the combination of isatuximab with cemiplimab. - To evaluate the safety of the combination of isatuximab with cemiplimab and radiotherapy in patients with cHL. - To evaluate the immunogenicity of isatuximab and cemiplimab when given in combination. - To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab when given in combination. - To assess overall efficacy of isatuximab in combination with cemiplimab and isatuximab in combination with cemiplimab and radiotherapy.

Detailed Description

      The total study duration per patient is up to 28 months, including an up to 28-day screening
      period, an up to 96-week treatment period, and a 90-day safety follow up period.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: cHl/DLBCL/PTCLExperimentalIsatuximab dose 1 or 2 depending on dose limiting toxicities (DLTs) observed and cemiplimab predefined dose
  • isatuximab SAR650984
  • cemiplimab REGN2810
Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïveExperimentalIsatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
  • isatuximab SAR650984
  • cemiplimab REGN2810
Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressorExperimentalIsatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
  • isatuximab SAR650984
  • cemiplimab REGN2810
Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïveExperimentalIsatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
  • isatuximab SAR650984
  • cemiplimab REGN2810
Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïveExperimentalIsatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
  • isatuximab SAR650984
  • cemiplimab REGN2810

Eligibility Criteria

        Inclusion criteria:

          -  Participants must be ≥ 12 years of age inclusive, at the time of signing the informed
             consent

          -  Disease location amenable to tumor biopsy at baseline

          -  Measurable disease

          -  For Cohort A1 (classic Hodgkin's lymphoma [cHL] anti-programmed cell death protein
             1/ligand 1 [PD-1/PD-L1] inhibitor naïve): Histologically confirmed advanced cHL that
             has relapsed or progressed after at least 3 lines of systemic therapy that may include
             autologous hematopoietic stem cell transplant (auto-HSCT) or auto-HSCT and brentuximab
             vedotin (BV)

          -  For Cohort A2 (cHL anti-PD-1/PD-L1 inhibitor progressor): Histologically confirmed
             advanced cHL which has relapsed or progressed after one previous anti-PD-1/PD-L1
             containing regimen as the most recent prior therapy but no more than 4 lines of
             previous chemotherapy including the anti-PD-1/PD-L1 containing regimen and
             documentation of benefit during or after the anti-PD-1/PD-L1 containing regimen within
             4 months prior to initiation of investigational medicinal product (IMP)

          -  For Cohort B (diffuse large B-cell lymphoma [DLBCL]): Histologically confirmed
             advanced DLBCL that has relapsed or progressed after 2 lines of systemic therapy
             including auto-HSCT or 2 lines of systemic therapy for participants who are not
             eligible for auto-HSCT

          -  For Cohort C (peripheral T-cell lymphoma [PTCL]): Histologically confirmed advanced
             PTCL that has relapsed or progressed after either first-line chemotherapy and
             auto-HSCT as consolidation of first remission or first-line chemotherapy if
             participants are ineligible for auto-HSCT

          -  Body weight of > 45 kg for patients with age <18 years

        Exclusion criteria:

          -  Prior exposure to agent that blocks CD38

          -  For patients with cHL (PD-1/PD-L1 naïve), DLBCL or PTCL prior exposure to any agent
             (approved or investigational) that blocks the PD-1/PD-L1, PD-L2, CD137, CTLA-4 or
             LAG-3

          -  Evidence of other immune related disease/conditions

          -  Has received a live-virus vaccination within 28 days of planned treatment start;
             seasonal flu vaccines that do not contain live virus are permitted

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2

          -  Poor bone marrow reserve

          -  Poor organ function

        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:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 - Dose limiting toxicities (DLTs); Recommended Phase 2 dose (RP2D)
Time Frame:1st Cycle - 28 days
Safety Issue:
Description:DLTs as observed during DLT-observation period; Dose selected for the Phase 2 portion

Secondary Outcome Measures

Measure:Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab
Time Frame:Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)
Safety Issue:
Description:Number of patients with AEs/SAEs
Measure:Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy
Time Frame:Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration)
Safety Issue:
Description:Number of patients with AEs/SAEs in cohorts A1 and A2
Measure:Immunogenicity: Anti-drug antibody levels
Time Frame:Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
Safety Issue:
Description:Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab
Measure:Pharmacokinetic evaluation: Cmax
Time Frame:Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
Safety Issue:
Description:Maximum concentration observed after the first infusion
Measure:Pharmacokinetic evaluation: Ctrough
Time Frame:Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
Safety Issue:
Description:Concentrations observed just before treatment administration during repeated dosing
Measure:Pharmacokinetic evaluation: AUC0-T
Time Frame:Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first
Safety Issue:
Description:Area under the concentration versus time curve calculated using the trapezoidal method over the dosing interval (ie, 6 days for isatuximab or 21 days for cemiplimab)
Measure:Tumor burden change
Time Frame:Up to 24 weeks after last patient treated in a given cohort
Safety Issue:
Description:The best percent-change from baseline
Measure:Disease control rate
Time Frame:Up to 24 weeks after last patient treated in a given cohort
Safety Issue:
Description:The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
Measure:Duration of response
Time Frame:Up to 24 weeks after last patient treated in a given cohort
Safety Issue:
Description:The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first
Measure:Progression free survival
Time Frame:Up to 24 weeks after last patient treated in a given cohort
Safety Issue:
Description:The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

December 13, 2019