SAR650984, Lenalidomide, and Dexamethasone in Combination in RRMM Patients
To determine the maximum tolerated dose of SAR650984 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 in combination with LD using International Myeloma Working Group (IMWG) criteria.
To evaluate the safety, including immunogenicity, of SAR650984 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 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 escalation phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 plus LD.
To describe progression-free survival (PFS) in patients treated with this combination.
|Study Design:||Intervention Model: Parallel Assignment
Masking: Open Label
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 in combination with LD [ Time Frame: Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment ] [ Designated as safety issue: Yes ]
- Preliminary assessment of overall response rate [ Time Frame: 12 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration ] [ Designated as safety issue: No ]
- Preliminary assessment of progression-free survival (PFS) [ Time Frame: Up to disease progression ] [ Designated as safety issue: No ]
- Assessment of PK parameters - maximum concentration (Cmax) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
- Assessment of PK parameters - time to reach Cmax (Tmax) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
- Assessment of PK parameters - concentration observed at end of infusion (Ceoi) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Assessment of PK parameters - plasma concentration observed just before treatment administration during repeated dosing (Ctrough) [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
- Number of CD38 receptors occupied by SAR650984 [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
- CD38 receptor density [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
- Immunogenicity: Number of anti-SAR650984 antibodies in response to SAR650984 [ Time Frame: Up to disease progression plus 60 days ] [ Designated as safety issue: No ]
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
SAR650984 (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 on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle
Pharmaceutical form:capsules Route of administration: oral
Other Name: RevlimidDrug: dexamethasone
Pharmaceutical form:solution or tablet Route of administration: intravenous or oralDrug: SAR650984
Pharmaceutical form:solution Route of administration: intravenous
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749969
|Contact: For site information, send an email with site number to||Contact-Us@sanofi.com|
|United States, California|
|Investigational Site Number 840004||Recruiting|
|San Francisco, California, United States, 94117|
|United States, Florida|
|Investigational Site Number 840001||Recruiting|
|Tampa, Florida, United States, 33612|
|United States, Missouri|
|Investigational Site Number 840002||Active, not recruiting|
|St Louis, Missouri, United States, 63110|
|United States, New York|
|Investigational Site Number 840005||Recruiting|
|New York, New York, United States, 10021|
|United States, Ohio|
|Investigational Site Number 840003||Recruiting|
|Columbus, Ohio, United States, 43210|
|Study Director:||Clinical Sciences & Operations||Sanofi|