Haematological malignancy MedDRA version: 21.1 Level: PT Classification code 10066476 Term: Haematological malignancy System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1: -For dose escalation cohorts, patients with confirmed selected CD38+ haematological malignancies as specified below who have progressed on after standard therapy or for whom there is no effective standard therapy (refractory/relapsed patients). B-cell Non-Hodgkin-lymphoma/leukemia (NHL) patients having at least 1 measurable lesion. Multiple myeloma (MM) patients with measurable M-protein serum and/or 24-hour urine. Acute myeloid leukemia (AML) patients, all types except M3 based on French-American-British (FAB) classification. Acute lymphoblastic leukemia (B-cell ALL) patients. Chronic lymphocytic leukemia (CLL) patients. -For expansion cohorts, patients with relapsed/refractory MM with measurable M-protein (serum M-protein of >0.5 g/dL and/or urine M-protein of >200 mg [24-hr urine] or elevated serum free light chains [FLC] >10 mg/dL with abnormal FLC ratio) who have progressed on or after standard therapy that includes an IMiD and a proteasome inhibitor and who meet the protocol defined criteria for standard risk or high risk. Phase 2: -Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria: Serum M-protein =1 g/dL (=0.5 g/dL in case of IgA disease for stage 2), or urine M-protein =200 mg/24 hours or in the absence of measurable m-protein, serum FLC =10 mg/dL, and abnormal serum immunoglobulin kappa lambda FLC ratio (1.65). -Patients must have received at least three prior lines of therapy for MM and must include treatment with an Immunomodulatory drug (IMiD) (for =2 cycles or =2 months of treatment) and a proteasome inhibitor (PI) (for =2 cycles or =2 months of treatment) or patients whose disease is double refractory to an IMiD and a PI. For patients who have received more than 1 type of IMiD and PI, their disease must be refractory to the most recent one. -Patients must have achieved a minimal response or better to at least one prior line of therapy. -Patients must have received an alkylating agent (=2 cycles or =2 months) either alone or in combination with other MM treatments. -Stage 2 only : Patients must have evidence of disease progression on or after the most recent prior regimen based on IMWG criteria. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 171 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 170
Exclusion criteria
Exclusion criteria: Phase 1: - Karnofsky performance status 2 (stage 2) -Poor bone marrow reserve. -Poor organ function. -Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that is not amenable to pre-medication with steroids and H2 blockers. -Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results. -Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -Phase 1: To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (Isatuximab). -Phase 2 (stage 1): To evaluate the activity of single-agent Isatuximab at different doses/schedules and to select dose and regimen to further evaluate the overall response rate (ORR) of Isatuximab as single agent or in combination with dexamethasone. -Phase 2 (stage 2): To evaluate the activity in terms of overall response rate (ORR) of Isatuximab at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm).;Secondary Objective: Phase 1 - To characterize the global safety profile including cumulative toxicities - To evaluate the pharmacokinetic (PK) profile of isatuximab in the proposed dosing schedule(s) - To assess the pharmacodynamics (PD), immune response, and preliminary disease response Phase 2 (stage 1) : to evaluate the followings objectives for Isatuximab as single agent: - Safety - Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival Phase 2 (stage 2) : to evaluate the followings objectives in each arm (ISA and ISAdex): - Safety - Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival ;Primary end point(s): Dose Limiting Toxicities (DLTs) Overall Response Rate ;Timepoint(s) of evaluation of this end point: Dose Limiting Toxicities (DLTs) : 4 weeks Overall Response Rate : 4 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - 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. 2 - Main PK parameters: Area under the serum concentration time curve (AUC), maximum observed concentration (Cmax), Time to reach Cmax (tmax) 3 - Main PD Biomarker: CD38 receptor occupancy and receptor density 4 - Immune response: levels of human anti-human antibodies 5 - Duration of Response 6 - Patient reported outcomes 7 - Overall Survival 8 - Clinical Benefit Rate 9 - Progression Free Survival;Timepoint(s) of evaluation of this end point: 1 - Up to end of treatment + 30 days, up to a maximum study duration of 36 months 2 - up to end of treatment + 60 days 3 - Up to end of treatment 4 - Up to end of treatment + 60 days 5 - 12 months from last patient in 6 - every 4 weeks up to end of treatment 7 - 8 - 9 - 12 months from last patient in | — |
Countries
Argentina, Austria, Belgium, Brazil, Chile, Colombia, Finland, Greece, Israel, Italy, Mexico, Peru, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactMedical Information
Sanofi-aventis recherche & développement
Outcome results
None listed