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A Study of Isatuximab-based Therapy in Participants With Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03769181
Recruitment Status : Active, not recruiting
First Posted : December 7, 2018
Last Update Posted : October 20, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE November 29, 2018
First Posted Date  ICMJE December 7, 2018
Last Update Posted Date October 20, 2020
Actual Study Start Date  ICMJE December 11, 2018
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2019)
  • Phase 1 - Dose limiting toxicities (DLTs); Recommended Phase 2 dose (RP2D) [ Time Frame: 1st Cycle - 28 days ]
    DLTs as observed during DLT-observation period; Dose selected for the Phase 2 portion
  • Phase 2 - Cohort A1 (anti-PD-1/PD-L1 naive cHL): Complete Remission Rate [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The proportion of participants who have a Complete Remission as a best overall response during the isatuximab + cemiplimab therapy period using the Lugano response criteria 2014
  • Phase 2 - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): Response Rate [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The proportion of participants who have a Complete Response or Partial Response as a best overall response during isatuximab + cemiplimab therapy period using the Lugano response criteria 2014
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • Phase 1 - Dose limiting toxicities (DLTs); Recommended Phase 2 dose (RP2D) [ Time Frame: 1st Cycle - 28 days ]
    DLTs as observed during DLT-observation period; Dose selected for the Phase 2 portion
  • Phase 2 - Cohort A1 (anti-PD-1/PD-L1 naive cHL): Complete Remission Rate [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The proportion of participants who have a Complete Remission as a best overall response during the isatuximab + cemiplimab therapy period using the 5-point scale per the Lugano classification where 1 is No uptake, 2 is Uptake ≤ mediastinum, 3 is Uptake > mediastinum but ≤ liver, 4 is Moderately increased uptake compared to the liver and 5 is Markedly increased uptake compared to the liver and/or new lesions
  • Phase 2 - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): Response Rate [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The proportion of participants who have a Complete Response or Partial Response as a best overall response during isatuximab + cemiplimab therapy period using the 5-point scale per the Lugano classification where 1 is No uptake, 2 is Uptake ≤ mediastinum, 3 is Uptake > mediastinum but ≤ liver, 4 is Moderately increased uptake compared to the liver and 5 is Markedly increased uptake compared to the liver and/or new lesions
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2018)
  • 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) ]
    Number of patients with AEs/SAEs
  • 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) ]
    Number of patients with AEs/SAEs in cohorts A1 and A2
  • 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 ]
    Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab
  • 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 ]
    Maximum concentration observed after the first infusion
  • 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 ]
    Concentrations observed just before treatment administration during repeated dosing
  • 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 ]
    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)
  • Tumor burden change [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The best percent-change from baseline
  • Disease control rate [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
  • Duration of response [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    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
  • Progression free survival [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Isatuximab-based Therapy in Participants With Lymphoma
Official Title  ICMJE 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
Brief Summary

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Drug: isatuximab SAR650984

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

    Other Name: Sarclisa
  • Drug: cemiplimab REGN2810

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

Study Arms  ICMJE
  • Experimental: Phase 1: cHl/DLBCL/PTCL
    Isatuximab dose 1 or 2 depending on dose limiting toxicities (DLTs) observed and cemiplimab predefined dose
    Interventions:
    • Drug: isatuximab SAR650984
    • Drug: cemiplimab REGN2810
  • Experimental: Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve
    Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
    Interventions:
    • Drug: isatuximab SAR650984
    • Drug: cemiplimab REGN2810
  • Experimental: Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor
    Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
    Interventions:
    • Drug: isatuximab SAR650984
    • Drug: cemiplimab REGN2810
  • Experimental: Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve
    Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
    Interventions:
    • Drug: isatuximab SAR650984
    • Drug: cemiplimab REGN2810
  • Experimental: Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve
    Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose
    Interventions:
    • Drug: isatuximab SAR650984
    • Drug: cemiplimab REGN2810
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 5, 2018)
130
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Italy,   Korea, Republic of,   Netherlands,   Portugal,   Spain,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03769181
Other Study ID Numbers  ICMJE ACT15320
2018-002442-37
U1111-1211-9010 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP