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Study of Isatuximab Combined With Bortezomib + Cyclophosphamide + Dexamethasone (VCD) and Bortezomib + Lenalidomide + Dexamethasone (VRD) in Newly Diagnosed Multiple Myeloma (MM) Non Eligible for Transplant or No Intent for Immediate Transplantation

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ClinicalTrials.gov Identifier: NCT02513186
Recruitment Status : Recruiting
First Posted : July 31, 2015
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE July 16, 2015
First Posted Date  ICMJE July 31, 2015
Last Update Posted Date November 20, 2019
Actual Study Start Date  ICMJE September 30, 2015
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • Assessment of dose-limiting toxicities (DLTs) in VCDI cohort [ Time Frame: Up to 6 weeks per treated patient ]
  • Overall response rate (VCDI) [ Time Frame: Up to 34 weeks of treatment (induction phase) ]
  • Complete response rate (VCDI) [ Time Frame: Up to 34 weeks of treatment (induction phase) ]
  • Complete response rate (VRDI) [ Time Frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 30, 2015)
Assessment of dose-limiting toxicities (DLTs) [ Time Frame: Up to 6 weeks ]
Change History Complete list of historical versions of study NCT02513186 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2019)
  • Number of patients with adverse events (AEs), clinically significant changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling [ Time Frame: VCDI: Up to approximately 106 weeks, VRDI Part A and Part B: Up to approximately 104 weeks ]
  • Overall response rate (VRDI) [ Time Frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
  • Infusion duration [ Time Frame: VRDI Part B: Up to 104 weeks of treatment ]
  • Assessment of PK parameter: Partial area under the serum concentration time curve (AUC) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
  • Assessment of PK parameter: Maximum observed concentration (Cmax) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
  • Levels of human antidrug antibodies (ADA) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
  • Duration of response - time [ Time Frame: VCDI and VRDI: Until treatment discontinuation by the last patient ]
  • Progression-free survival for VCDI [ Time Frame: VCDI: 30 months after LPI ]
  • Progression-free survival for VRDI [ Time Frame: VRDI Part A and Part B: 24 months after LPI ]
  • MRD negativity rate [ Time Frame: Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 30, 2015)
  • Overall response rate [ Time Frame: Up to 50 weeks of treatment (induction phase) ]
  • Number of patients with adverse events (AEs) [ Time Frame: Up to approximatively 106 weeks (50 wks for induction phase, 52 wks for maintenance phase;30 days for post-treatment phase) ]
  • Number of patients with clinically significant changes in laboratory tests according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.0 grade scaling [ Time Frame: Up to approximatively 106 weeks (50 wks for induction phase, 52 wks for maintenance phase;30 days for post-treatment phase) ]
  • Number of patients with clinically significant changes in vital signs according to the NCI-CTC version 4.0 grade scaling [ Time Frame: Up to approximatively 106 weeks (50 wks for induction phase, 52 wks for maintenance phase;30 days for post-treatment phase) ]
  • Assessment of PK parameter: Partial area under the serum concentration time curve (AUC) [ Time Frame: Up to approximatively 110 weeks (50 wks for induction phase, 52 wks for maintenance phase;60 days for post-treatment phase) ]
  • Assessment of PK parameter: Maximum observed concentration (Cmax) [ Time Frame: Up to approximatively 110 weeks (50 wks for induction phase, 52 wks for maintenance phase;60 days for post-treatment phase) ]
  • Levels of human antidrug antibodies (ADA) [ Time Frame: Up to approximatively 110 weeks (50 wks for induction phase, 52 wks for maintenance phase;60 days for post-treatment phase) ]
  • Duration of response - time [ Time Frame: Up to approximatively 154 weeks (102 wks for treatment phase; plus approximatively 1-year follow up until progression or death, whichever came first) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Isatuximab Combined With Bortezomib + Cyclophosphamide + Dexamethasone (VCD) and Bortezomib + Lenalidomide + Dexamethasone (VRD) in Newly Diagnosed Multiple Myeloma (MM) Non Eligible for Transplant or No Intent for Immediate Transplantation
Official Title  ICMJE A Dose Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of SAR650984 (Isatuximab) Administered Intravenously in Combination With Bortezomib - Based Regimens in Adult Patients With Newly Diagnosed Multiple Myeloma Non Eligible for Transplantation or No Intent for Immediate Transplantation
Brief Summary

Primary Objectives:

VCDI cohort:

  • To determine the maximum tolerated dose (MTD) and recommended dose (RD) of isatuximab when administered in combination with bortezomib, cyclophosphamide, and dexamethasone (VCDI) based on the dose-limiting toxicity(ies) (DLTs) observed in patients with newly diagnosed multiple myeloma non-eligible for transplantation.
  • To evaluate safety and preliminary efficacy (overall response rate and complete response rate) of isatuximab in combination with bortezomib, dexamethasone, and cyclophosphamide in patients with newly diagnosed multiple myeloma non-eligible for transplantation.

VRDI cohort parts A and B:

  • To evaluate preliminary efficacy (complete response rate) of isatuximab in combination with bortezomib, dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma non-eligible for transplantation or no intent for immediate transplantation.

Secondary Objectives:

  • To characterize the overall safety profile of isatuximab in combination with each bortezomib-based regimen, including cumulative toxicities.
  • To characterize the pharmacokinetic (PK) profile of isatuximab and each combination drug in each isatuximab/bortezomib based regimen.
  • To evaluate the immunogenicity of isatuximab in combination treatments.
  • To evaluate the preliminary efficacy of both bortezomib based regimens in terms of duration of response, overall response rate and progression-free survival.
  • To assess the relationship between clinical effects (adverse event [AE] and/or tumor response) and CD38 receptor density (VCDI and VRDI part only).
  • To evaluate the infusion duration.
  • To assess the minimal residual disease (MRD) negativity rate in patients achieving a Complete Response (CR) or Very Good Partial Response (VGPR).
Detailed Description

The duration of the study for an individual patient will include:

  • A period to assess eligibility (screening or baseline period) of up to 3 weeks for VCDI cohort, up to 28 days for VRDI cohort;
  • for patients in the VCDI cohort: a treatment period including up to 12 induction treatment cycles (50-week duration).
  • for patients in the VRDI cohort: a treatment period including up to 4 induction cycles (24 week duration).
  • Following induction, both cohorts have maintenance periods consisting of 4 week cycles until progression, unacceptable AE, or patient willingness to discontinue and an end-of-treatment visit at least 30 days following the last administration of treatment.
  • Patients that discontinue therapy for reasons other than progression will have follow-up visits until progression or until the patient receives another anticancer therapy, whichever is earlier.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Plasma Cell Myeloma
Intervention  ICMJE
  • Drug: lenalidomide
    Pharmaceutical form: tablet Route of administration: oral
    Other Name: Revlimid
  • Drug: bortezomib
    Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous
    Other Name: Velcade
  • Drug: cyclophosphamide
    Pharmaceutical form: tablet Route of administration: oral
    Other Name: Endoxan
  • Drug: dexamethasone
    Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous
  • Drug: isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
Study Arms  ICMJE Experimental: Isatuximab

VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.

VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.

VRDI Part A: Enrollment to begin after the VCDI cohort is completed.

VRDI Part B: Enrollment to begin after the VRDI part A is completed.

Interventions:
  • Drug: lenalidomide
  • Drug: bortezomib
  • Drug: cyclophosphamide
  • Drug: dexamethasone
  • Drug: isatuximab SAR650984
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2019)
88
Original Estimated Enrollment  ICMJE
 (submitted: July 30, 2015)
18
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

Newly diagnosed patients with measurable multiple myeloma defined as at least one of the following:

  • Serum M protein ≥1 g/dL (≥10 g/L).
  • Urine M protein ≥200 mg/24 hours.
  • Serum free light chain (sFLC) assay: involved free light chain assay ≥10 mg/dL (≥100 mg/L) and an abnormal sFLC ratio (<0.26 or >1.65).

Patients with ultra-high risk smoldering multiple myeloma fulfilling the International Myeloma Working Group criteria are eligible.

Patient is not eligible for transplant.

Patient with no immediate intent for transplant as per investigator's decision are also eligible for VRDI Part B cohort only.

Exclusion criteria:

Eastern Cooperative Oncology Group performance status >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 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com
Listed Location Countries  ICMJE France,   Germany,   Italy,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02513186
Other Study ID Numbers  ICMJE TCD13983
2014-001251-23 ( EudraCT Number )
U1111-1154-6102 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: 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 November 2019

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