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

• ClinicalTrials.gov Identifier: NCT02513186
• Recruitment Status: Recruiting
• First Posted: July 31, 2015
• Last Update Posted: October 14, 2019
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Plasma Cell Myeloma	Drug: lenalidomide; Drug: bortezomib; Drug: cyclophosphamide; Drug: dexamethasone; Drug: isatuximab SAR650984	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 88 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 30, 2015
• Estimated Primary Completion Date: October 2022
• Estimated Study Completion Date: October 2022

Arms and Interventions

Arm

Intervention/treatment

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.

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

Outcome Measures

Primary Outcome Measures :

1. Assessment of dose-limiting toxicities (DLTs) in VCDI cohort [ Time Frame: Up to 6 weeks per treated patient ]
2. Overall response rate (VCDI) [ Time Frame: Up to 34 weeks of treatment (induction phase) ]
3. Complete response rate (VCDI) [ Time Frame: Up to 34 weeks of treatment (induction phase) ]
4. Complete response rate (VRDI) [ Time Frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]

Secondary Outcome Measures :

1. 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 ]
2. Overall response rate (VRDI) [ Time Frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]
3. Infusion duration [ Time Frame: VRDI Part B: Up to 104 weeks of treatment ]
4. 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 ]
5. Assessment of PK parameter: Maximum observed concentration (Cmax) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
6. Levels of human antidrug antibodies (ADA) [ Time Frame: VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks ]
7. Duration of response - time [ Time Frame: VCDI and VRDI: Until treatment discontinuation by the last patient ]
8. Progression-free survival for VCDI [ Time Frame: VCDI: 30 months after LPI ]
9. Progression-free survival for VRDI [ Time Frame: VRDI Part A and Part B: 24 months after LPI ]
10. MRD negativity rate [ Time Frame: Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

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

Locations

France

Investigational Site Number 250002; Recruiting

Nantes Cedex 01, France, 44093

Investigational Site Number 250003; Recruiting

Pierre Benite, France, 69495

Investigational Site Number 250001; Recruiting

Toulouse Cedex 9, France, 31059

Germany

Investigational Site Number 276003; Recruiting

Berlin, Germany, 12200

Investigational Site Number 276002; Recruiting

Leipzig, Germany, 04103

Italy

Investigational Site Number 380003; Recruiting

Milano, Italy, 20132

Investigational Site Number 380002; Recruiting

Roma, Italy, 00161

Investigational Site Number 380001; Recruiting

Torino, Italy, 10126

Spain

Investigational Site Number 724003; Recruiting

Madrid, Spain, 28041

Investigational Site Number 724001; Recruiting

Pamplona, Spain, 31008

Investigational Site Number 724002; Recruiting

Salamanca, Spain, 37007

Investigational Site Number 724004; Recruiting

Santander, Spain, 39008

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02513186 History of Changes
• Other Study ID Numbers: TCD13983; 2014-001251-23 ( EudraCT Number ); U1111-1154-6102 ( Other Identifier: UTN )
• First Posted: July 31, 2015
• Last Update Posted: October 14, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• 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

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Lenalidomide; Bortezomib; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal