Phase 1/2 Dose Escalation and Efficacy Study of Anti-CD38 Monoclonal Antibody in Patients With Selected CD38+ Hematological Malignancies
To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984.
To evaluate the activity of single-agent SAR650984 at different doses/schedules and to further evaluate the overall response rate (ORR) of SAR650984 at the selected dose.
- To characterize the global safety profile including cumulative toxicities.
- To evaluate the pharmacokinetic (PK) profile of SAR650984 in the proposed dosing schedule(s).
- To assess the pharmacodynamics (PD), immune response, and preliminary disease response.
- To evaluate safety of SAR650984.
- To evaluate the efficacy of SAR650984 as measured by duration of response, clinical benefit rate, progression free survival, overall survival.
- To evaluate patient reported outcomes.
- To evaluate the PK profile.
- To evaluate the immunogenicity of SAR650984.
- To investigate the relationship between CD38 receptor occupancy and CD38 receptor density and parameters of clinical response.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies|
- Dose Limiting Toxicities (DLTs) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
- Overall Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
- Safety as assessed from adverse events reporting, laboratory tests, vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.0 grade scaling [ Time Frame: Up to end of treatment + 30 days, up to a maximum study duration of 36 months ] [ Designated as safety issue: Yes ]
- Main PK parameters : Partial area under the serum concentration time curve (AUC), maximum observed concentration (Cmax) [ Time Frame: Up to end of treatment + 60 days ] [ Designated as safety issue: No ]
- Main PD Biomarker : CD38 receptor occupancy and receptor density [ Time Frame: Up to end of treatment ] [ Designated as safety issue: No ]
- Immune response : levels of human anti-human antibodies [ Time Frame: Up to end of treatment + 60 days ] [ Designated as safety issue: Yes ]
- Duration of Response [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
- Patient reported outcomes [ Time Frame: Every 4 weeks up to end of treatment ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
- Clinical Benefit Rate [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
- Progression Free Survival [ Time Frame: 12 months from last patient in ] [ Designated as safety issue: No ]
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||August 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Phase 1: Accelerated dose escalation phase (1 patient/cohort), two administrations every two weeks (Q2W) per dose cohort. Followed by basic dose escalation phase evaluating SAR650984 administration weekly (QW) and Q2W with 3-6 patients/cohort treated until disease progression or unsatisfactory safety. Cohort 1-10 will enroll patients with CD38+ hematological malignancies and cohort 11 onwards will enroll patients with multiple myeloma only. Two expansion cohorts will evaluate the recommended Phase 2 dose (RP2D) in standard risk and high risk multiple myeloma patients.
Phase 2: Stage 1 will further evaluate four randomized arms. Arm 1: Dose 1 Q2W, Arm 2: Dose 2 Q2W, Arm 3: Dose 2 Q2W for 2 cycles then every 4 weeks (Q4W), Arm 4: Dose 3 QW for 1 cycle then Q2W. Stage 2 will use the dose and schedule determined from Stage 1.
Pharmaceutical form: solution for infusion
Route of administration: intravenous
The Phase 1 study duration for an individual patient will include a screening period for inclusion of up to 2 weeks, treatment with SAR650984 QW (every week) or Q2W (every 2 weeks) unless discontinued earlier due to safety or disease progression. Patients will be followed for a minimum of 30 days following the last use of study drug or more than 30 days in case of unresolved toxicity, or up to initiation of another anticancer treatment.
The Phase 2 study duration for an individual patient will include a screening period for inclusion of up to 3 weeks, treatment with SAR650984 Q2W or Q4W (every 4 weeks) unless discontinued earlier due to safety or disease progression. Patients will be followed every 3 months following the last use of study drug until death or study cutoff whichever comes first.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01084252
|Contact: For site information, send an email with site number to||Contact-Us@sanofi.com|
|United States, Arizona|
|Investigational Site Number 840003||Recruiting|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, California|
|Investigational Site Number 840005||Recruiting|
|San Francisco, California, United States, 94117|
|United States, Georgia|
|Investigational Site Number 840009||Recruiting|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|Investigational Site Number 840010||Recruiting|
|Chicago, Illinois, United States, 60637|
|United States, Michigan|
|Investigational Site Number 840022||Recruiting|
|Ann Arbor, Michigan, United States, 48109-0759|
|Investigational Site Number 840027||Recruiting|
|Detroit, Michigan, United States, 48201|
|United States, Missouri|
|Investigational Site Number 840013||Recruiting|
|St Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Investigational Site Number 840011||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|United States, Ohio|
|Investigational Site Number 840004||Completed|
|Cincinnati, Ohio, United States, 45267-0542|
|United States, Tennessee|
|Investigational Site Number 840001||Recruiting|
|Nashville, Tennessee, United States, 37232|
|United States, Utah|
|Investigational Site Number 840002||Recruiting|
|Salt Lake City, Utah, United States, 84112-5550|
|United States, Washington|
|Investigational Site Number 840012||Recruiting|
|Seattle, Washington, United States, 98109|
|Investigational Site Number 250003||Recruiting|
|Nantes Cedex 01, France, 44093|
|Investigational Site Number 250004||Recruiting|
|Pierre Benite, France, 69310|
|Investigational Site Number 250001||Recruiting|
|Toulouse, France, 31052|
|Investigational Site Number 724002||Recruiting|
|Pamplona, Spain, 31008|
|Investigational Site Number 724001||Recruiting|
|Salamanca, Spain, 37007|
|Study Director:||Clinical Sciences & Operations||Sanofi|