SAR650984 (Isatuximab), Lenalidomide, and Dexamethasone in Combination in RRMM Patients
- Conditions
- Plasma Cell Myeloma
- Interventions
- Registration Number
- NCT01749969
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objectives:
* To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma.
* Expansion Phase Only: To further evaluate preliminary evidence of antitumor activity (objective response rate \[ORR\]) of SAR650984 (isatuximab) in combination with LD using International Myeloma Working Group (IMWG) criteria.
Secondary Objectives:
* To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, frequency and incidence of all toxicities will be assessed.
* To evaluate the pharmacokinetics (PK) of SAR650984 (isatuximab) when administered in combination with LD and the PK of lenalidomide in combination with SAR650984 and dexamethasone.
* To assess the relationship between clinical (adverse event \[AE\] and/or tumor response) effects and pharmacologic parameters (PK/pharmacodynamics), and/or biologic (correlative laboratory) results.
* For the dose expansion phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 (isatuximab) plus LD.
* To describe progression-free survival (PFS) in patients treated with this combination.
- Detailed Description
The study duration for an individual patient will include a screening period for inclusion of up to 21 days, and at least 4 weeks of treatment in the absence of severe adverse reaction, dose limiting toxicity or disease progression plus up to 60 days post-treatment follow up. The treatment period may continue until disease progression, intolerable toxicity, or Investigator, sponsor, or patient decision to discontinue therapy. After study treatment discontinuation, an end of treatment (EOT) visit will be done at 30 days to assess safety, and at 30 and 60 days for anti-drug antibody (ADA) and PK. If the ADA is positive or inconclusive at day 60, then PK and ADA will be repeated every 30 days until ADA is negative. Patients who discontinue treatment for reasons other than progression of disease will be followed monthly until progression, initiation of subsequent therapy, or until the primary analysis cutoff date, whichever comes first.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR650984 (isatuximab) isatuximab SAR650984 SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression. For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle. SAR650984 (isatuximab) lenalidomide SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression. For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle. SAR650984 (isatuximab) dexamethasone SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression. For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle.
- Primary Outcome Measures
Name Time Method Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment
- Secondary Outcome Measures
Name Time Method CD38 receptor density Up to disease progression plus 60 days Assessment of PK parameters - maximum concentration (Cmax) Up to disease progression plus 60 days Assessment of PK parameters - concentration observed at end of infusion (Ceoi) Up to disease progression plus 60 days Preliminary assessment of progression-free survival (PFS) Up to disease progression Preliminary assessment of overall response rate 9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough) Up to disease progression plus 60 days Number of CD38 receptors occupied by SAR650984 (isatuximab) Up to disease progression plus 60 days Assessment of PK parameters - time to reach Cmax (Tmax) Up to disease progression plus 60 days Assessment of PK parameters - area under the plasma concentration versus time curve over the dosing interval (AUCtau) Up to disease progression plus 60 days Immunogenicity: Number of anti-SAR650984 (isatuximab) antibodies in response to SAR650984 (isatuximab) Up to disease progression plus 60 days
Trial Locations
- Locations (5)
Investigational Site Number 840004
🇺🇸San Francisco, California, United States
Investigational Site Number 840003
🇺🇸Columbus, Ohio, United States
Investigational Site Number 840001
🇺🇸Tampa, Florida, United States
Investigational Site Number 840002
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 840005
🇺🇸New York, New York, United States