Leukaemia MedDRA version: 20.1 Level: PT Classification code 10024288 Term: Leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: SAR440234
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: CD3-CD123 TCE
Current Sponsor code: SAR440234
Concentration unit: mg milligram(s)
Concentratio
Sponsors
Sanofi-Aventis Recherche & Développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Confirmed diagnosis of Acute Myeloblastic leukemia (AML) (except acute promyelocytic leukemia), or myelodysplastic syndrome (MDS) with a risk category of intermediate or higher. - Patients with AML must be unlikely to benefit from cytotoxic chemotherapy. - Patients with B-ALL (B acute lymphoid leukemia) in second or subsequent relapse. - Patients with HR-MDS (high risk myelodysplastic syndrome) must have received =1 cycle of hypomethylating therapy or induction therapy and have =10% bone marrow blasts. - Signed written informed consent. Are the trial subjects under 18? yes Number of subjects for this age range: 5 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 32 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: - Age 2. - Patients with inadequate biological tests. - Graft-versus-host disease following allogeneic stem cell transplantation requiring treatment with more than 10 mg of oral prednisone or equivalent daily. The stem cell transplant and/or donor lymphocyte infusion should have been performed more than 3 months before study treatment start. - Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed. - Previous treatment with radiotherapy or immunotherapeutic agents in the 4 weeks prior to IMP administration - Previous treatment with any other investigational agent in the 4 weeks prior to IMP administration - Receiving, at the time of first IMP administration, of concurrent steroids >10 mg/day of oral prednisone or the equivalent for =3 months - Requirement for tociluzimab for any other diagnosis. - Evidence of active central nervous system leukemia at the time of enrollment. - Acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment. - Active hepatitis B viral infection or hepatitis C viral infection; HIV infection. - Women of childbearing potential, male with a partner of childbearing potential who do not agree to use effective methods of birth control. - Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Dose escalation: To determine the maximum tolerated dose (MTD) of SAR440234 administered as a single agent in patients with R/R AML (relapsed or refractory acute myeloid leukemia), HR-MDS (high risk myelodysplastic syndrome), or B-ALL (B-cell acute lymphoblastic leukemia), and determine the recommended phase 2 dose (RP2D) for the subsequent Expansion part. - Expansion part: To assess the activity of single agent SAR440234 at the RP2D in patients with R/R AML or HR-MDS.;Secondary Objective: -To characterize the safety profile including cumulative adverse drug reactions. -To evaluate the potential immunogenicity of SAR440234. -To assess any preliminary evidence of hematologic response in the Dose Escalation Part.;Primary end point(s): 1) Dose-limiting toxicities (DLTs): Incidence of DLTs observed, using NCI-CTCAE v4.03, during the first 42 days following the first administration of IMP in the first cycle of treatment. 2) Incidence of allergic reactions/hypersensitivity and CRS/acute infusion reactions: Incidence of allergic reactions/hypersensitivity and CRS/acute infusion reactions 3) Overall response rate (ORR): ORR is defined as the proportion of patients with complete response (CR), CRi, and partial response (PR) 4) Duration of response (DOR): DOR is defined as the time from the date of the first response (=PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first 5) Event-free survival: Event-free survival is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause;Timepoint(s) of evaluation of this end point: 1) Baseline to Day 42 2) and 3) Baseline to 30 days after last study treatment administration 4) and 5) Baseline to date of first documentation of disease progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Adverse events: Number of adverse events 2) Preliminary Anti-leukemia Activity: Preliminary anti-leukemia activity as defined by IWG 2003 for MDS or AML or National Comprehensive Cancer Network (NCCN) for B-ALL. (Dose escalation part). 3) Immunogenicity of SAR440234: Anti-SAR440234 Antibodies (ADA) incidence is defined as the proportion of patients found to either have treatment induced ADA or boosted their pre-existing ADA response during the study.;Timepoint(s) of evaluation of this end point: 1) Baseline to 30 days after last study treatment administration 2) and 3) Baseline to approximately 3 months after the last entered patient | — |
Countries
France, United States
Contacts
Public ContactDirection des Opérations Ciniques
Sanofi-aventis France
Outcome results
None listed