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A Study of Isatuximab-based Therapy in Participants With Lymphoma

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ClinicalTrials.gov Identifier: NCT03769181
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

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.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: isatuximab SAR650984 Drug: cemiplimab REGN2810 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 11, 2018
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Phase 1: cHl/DLBCL/PTCL
Isatuximab dose 1 or 2 depending on dose limiting toxicities (DLTs) observed and cemiplimab predefined dose
Drug: isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


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
Drug: isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


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
Drug: isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


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
Drug: isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


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
Drug: isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous





Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. Tumor burden change [ Time Frame: Up to 24 weeks after last patient treated in a given cohort ]
    The best percent-change from baseline

  8. 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)

  9. 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

  10. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03769181


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com

Locations
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France
Investigational Site Number 2500006 Recruiting
Creteil Cedex, France, 94010
Investigational Site Number 2500005 Recruiting
Dijon, France, 21000
Investigational Site Number 2500004 Recruiting
Montpellier Cedex 5, France, 34295
Investigational Site Number 2500002 Recruiting
Nantes Cedex 01, France, 44093
Investigational Site Number 2500007 Recruiting
Pessac, France, 33600
Investigational Site Number 2500003 Recruiting
Pierre Benite, France, 69495
Italy
Investigational Site Number 3800002 Recruiting
Bologna, Italy, 40138
Investigational Site Number 3800006 Recruiting
Brescia, Italy, 25123
Investigational Site Number 3800003 Recruiting
Rozzano, Italy, 20089
Korea, Republic of
Investigational Site Number 4100001 Recruiting
Gangnam-Gu, Korea, Republic of, 06351
Investigational Site Number 4100002 Recruiting
Seoul, Korea, Republic of, 03080
Investigational Site Number 4100003 Recruiting
Seoul, Korea, Republic of, 06591
Netherlands
Investigational Site Number 5280001 Recruiting
Maastricht, Netherlands, 6229 HX
Portugal
Investigational Site Number 6200002 Recruiting
Coimbra, Portugal, 3000-075
Investigational Site Number 6200003 Recruiting
Porto, Portugal, 4200
Spain
Investigational Site Number 7240003 Recruiting
Barcelona, Spain, 08035
Investigational Site Number 7240005 Recruiting
Barcelona, Spain, 08036
Investigational Site Number 7240002 Recruiting
Hospitalet De Llobregat, Spain, 08907
Investigational Site Number 7240004 Recruiting
Madrid, Spain, 28040
Investigational Site Number 7240001 Recruiting
Salamanca, Spain, 37007
Taiwan
Investigational Site Number 1580003 Recruiting
Kaohsiung, Taiwan, 807
Investigational Site Number 1580002 Recruiting
Taichung, Taiwan, 40447
Investigational Site Number 1580001 Recruiting
Taipei, Taiwan, 100
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03769181     History of Changes
Other Study ID Numbers: ACT15320
2018‐002442‐37
U1111-1211-9010 ( Other Identifier: UTN )
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
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/

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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

Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents