Dose Escalation, Safety and Pharmacokinetic Study of SAR103168 in Patients Refractory/ Relapsed Acute Leukemias or High-risk Myelodysplastic Syndromes

Completed · Phase 1

Conditions studied: Acute Myelogenous Leukemia

In brief

Primary objectives: * To determine the maximum tolerated dose (MTD) of SAR103168 and to characterize the dose limiting toxicities (DLTs) in the proposed dose regimen * To evaluate the pharmacokinetic (PK) profile of SAR103168 Secondary objectives: * To characterize the global safety profile of SAR103168 * To evaluate preliminary anti-leukemia activity * To investigate the potential induction effect on CYP3A4 and persistence of this effect by using oral midazolam as a probe substrate in patients enrolled into the expanded cohort at the MTD * To determine the metabolic pathways of SAR103168 and identify the chemical structures of metabolites * To determine the potential impact of SAR103168 on the QTc interval in patients enrolled at the MTD

Key facts

Study ID: NCT00981240
Run by: Sanofi
People needed: 30
Starts: 2009-09-01
Expected to finish: 2012-02-01
Last updated by the study team: 2012-03-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients with refractory/relapsed acute leukemias or high-risk myelodysplastic syndromes with no curative option available including any of the following:
Patients with de novo or secondary acute myelogenous leukemia (AML) (except acute promyelocytic leukemia), meeting one of the following conditions:
Refractory or relapsed AML; In case of first relapse the CR duration should be less than 12 months. If the relapse failed at least one prior salvage attempt, the CR duration may be more than 12 months.
Into the expanded cohort at the MTD, previously untreated AML patients over age 60 with poor- risk cytogenetics who are not eligible for or do not accept induction chemotherapy may also be included.
Patients with refractory/relapsed acute lymphoblastic leukemia (ALL)
Patients with high-risk myelodysplastic syndrome (MDS) as defined by the International Prognostic Scoring System
Patients with chronic myeloid leukemia in blast phase (CML-BP)

You may not qualify if…

performance status > 2
Active uncontrolled central nervous system leukemia
Cytotoxic therapy within 2 weeks prior to the first dose of SAR103168. For the non cytotoxic agents/investigational drugs this washout period should be at least 2 weeks or at least 5 half-lives whichever is longer. Hydroxyurea must be stopped at least 24 hours prior to the first dose of SAR103168
Lack of recovery from toxicities from prior therapies to grade < 1
White blood cells > 30 x 10\^9/L prior to the first dose of SAR103168
Prior allogeneic stem cell transplantation or donor lymphocytes infusion within 3 months preceding the first dose of SAR103168
Any of the following within 6 months prior to the first dose of SAR103168:
Myocardial infarction, congestive heart failure, documented angina pectoris, arrhythmia requiring medication (in particular atrial fibrillation or flutter), severe conduction disorder (second or third atrio-ventricular block, pacemaker), coronary/peripheral artery bypass graft surgery
Arterial or venous thromboembolism, deep venous thrombosis
Left ventricular ejection fraction < 50% by echocardiography or multiple gated acquisition scan
Cardiac ischemia on 12-lead ECG
Baseline QTc-interval > 500 msec
Hypertension uncontrolled with appropriate therapy
Active infection (viral, bacterial or fungal) uncontrolled with appropriate therapy
Major surgery within 6 weeks prior to the first dose of SAR103168
Poor organ function defined by one of the following:
Total bilirubin > 1.5 x upper limit of normal (ULN) unless related to leukemia (i.e. hemolysis) or Gilbert's syndrome
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2.5 x ULN
Serum creatinine > 1.5 x ULN or calculated creatinine clearance < 50 mL/min
Patients under treatment with potent inhibitors of CYP3A4 unless these treatments may be stopped at least 3 days prior to the first dose of SAR103168
Patients under treatment with CYP3A4 or CYP2C9 inducers, unless these treatments may be stopped at least 3 days prior to the first dose of SAR103168
Pregnant or breast-feeding women or refusal to use adequate contraceptive method, when applicable.

Where it is running

Sanofi-Aventis Investigational Site Number 840003 — Atlanta, Georgia, United States
Sanofi-Aventis Investigational Site Number 840002 — New York, New York, United States
Sanofi-Aventis Investigational Site Number 840001 — Houston, Texas, United States

Full record on ClinicalTrials.gov

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