SAR650984 (Isatuximab), Lenalidomide, and Dexamethasone in Combination in RRMM Patients
- 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.
- 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.
|Plasma Cell Myeloma||Drug: isatuximab SAR650984 Drug: lenalidomide Drug: dexamethasone||Phase 1|
|Study Design:||Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1b Study of SAR650984 (Anti-CD38 mAb) in Combination With Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma|
- Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD [ Time Frame: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment ]
- Preliminary assessment of overall response rate [ Time Frame: 9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration ]
- Preliminary assessment of progression-free survival (PFS) [ Time Frame: Up to disease progression ]
- Assessment of PK parameters - maximum concentration (Cmax) [ Time Frame: Up to disease progression plus 60 days ]
- Assessment of PK parameters - time to reach Cmax (Tmax) [ Time Frame: Up to disease progression plus 60 days ]
- Assessment of PK parameters - concentration observed at end of infusion (Ceoi) [ Time Frame: Up to disease progression plus 60 days ]
- Assessment of PK parameters - area under the plasma concentration versus time curve over the dosing interval (AUCtau) [ Time Frame: Up to disease progression plus 60 days ]
- Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough) [ Time Frame: Up to disease progression plus 60 days ]
- Number of CD38 receptors occupied by SAR650984 (isatuximab) [ Time Frame: Up to disease progression plus 60 days ]
- CD38 receptor density [ Time Frame: Up to disease progression plus 60 days ]
- Immunogenicity: Number of anti-SAR650984 (isatuximab) antibodies in response to SAR650984 (isatuximab) [ Time Frame: Up to disease progression plus 60 days ]
|Actual Study Start Date:||February 6, 2013|
|Estimated Study Completion Date:||December 28, 2018|
|Estimated Primary Completion Date:||December 28, 2018 (Final data collection date for primary outcome measure)|
Experimental: SAR650984 (isatuximab)
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.
Drug: isatuximab SAR650984
Pharmaceutical form:solution Route of administration: intravenousDrug: lenalidomide
Pharmaceutical form:capsules Route of administration: oral
Other Name: RevlimidDrug: dexamethasone
Pharmaceutical form:solution or tablet Route of administration: intravenous or oral
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749969
|United States, California|
|Investigational Site Number 840004|
|San Francisco, California, United States, 94117|
|United States, Florida|
|Investigational Site Number 840001|
|Tampa, Florida, United States, 33612|
|United States, Missouri|
|Investigational Site Number 840002|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Investigational Site Number 840005|
|New York, New York, United States, 10021|
|United States, Ohio|
|Investigational Site Number 840003|
|Columbus, Ohio, United States, 43210|
|Study Director:||Clinical Sciences & Operations||Sanofi|