Description:
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).
Title
- Brief Title: 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: 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
Clinical Trial IDs
- ORG STUDY ID:
TCD13983
- SECONDARY ID:
2014-001251-23
- SECONDARY ID:
U1111-1154-6102
- NCT ID:
NCT02513186
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| lenalidomide | Revlimid | Isatuximab |
| bortezomib | Velcade | Isatuximab |
| cyclophosphamide | Endoxan | Isatuximab |
| dexamethasone | | Isatuximab |
| isatuximab SAR650984 | Sarclisa | Isatuximab |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Isatuximab | Experimental | 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. | - lenalidomide
- bortezomib
- cyclophosphamide
- dexamethasone
- isatuximab SAR650984
|
Eligibility 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Assessment of dose-limiting toxicities (DLTs) in VCDI cohort |
| Time Frame: | Up to 6 weeks per treated patient |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Overall response rate (VRDI) |
| Time Frame: | Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts |
| Safety Issue: | |
| Description: | |
| Measure: | Infusion duration |
| Time Frame: | VRDI Part B: Up to 104 weeks of treatment |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Assessment of PK parameter: Maximum observed concentration (Cmax) |
| Time Frame: | VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Levels of human antidrug antibodies (ADA) |
| Time Frame: | VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of response - time |
| Time Frame: | VCDI and VRDI: Until treatment discontinuation by the last patient |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival for VCDI |
| Time Frame: | VCDI: 30 months after LPI |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival for VRDI |
| Time Frame: | VRDI Part A and Part B: 24 months after LPI |
| Safety Issue: | |
| Description: | |
| Measure: | MRD negativity rate |
| Time Frame: | Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Sanofi |
Trial Keywords
- Anti-CD38 monoclonal antibody
Last Updated
June 4, 2020
