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Study Summary
No. 2009-0196:.......Leukemia......Farhad Ravandi-Kashani......Leukemia
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Study Summary Title
Study Summary
Number:
2009-0196
Study Title:A Dose Escalation Safety and Pharmacokinetic Study of SAR103168 Administered as a Single Agent by Intravenous Infusion, Once Daily for 5 Consecutive Days to Patients with Refractory/Relapsed Acute Myelogenous Leukemia
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Physician New Patient Referral
Name:Farhad Ravandi-KashaniPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7305
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Sanofi Aventis
Phase of Study:Phase IReturn
Visit:
daily for 5 and then weekly
Treatment
Agents:
SAR103168Home Care:None
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Only if admitted for other reasons
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerated dose
of SAR103168 when given to patients with AML. The safety of this drug will also
be studied.
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Study Objectives / Outcomes
Primary:
1. To determine the maximum tolerated dose (MTD) of SAR103168 and to characterize the dose limiting toxicities (DLTs) in the proposed dose regimen
2. To evaluate the pharmacokinetic (PK) profile of SAR103168

Secondary:
1. To characterize the global safety profile of SAR103168
2. To evaluate preliminary anti-leukemia activity
3. To evaluate the inhibition of STAT5 phosphorylation as a surrogate pharmacodynamic end point of activity
4. 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
5. To determine the metabolic pathways of SAR103168 and identify the chemical structures of metabolites
6. To determine the potential impact of SAR103168 on the QTc interval in
patients enrolled at the MTD
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Study Status Information
Study Activation / Registration Date:08/28/2009
IRB Review and Approval Date:07/16/2009
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:40
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients with AML (except acute promyelocytic leukemia) meeting one of the following conditions: Refractory or relapsed AML; In case of first relapse the complete remission (CR) duration should be less than 12 months. If relapse failed at least one prior salvage attempt, the CR duration may be more than 12 months. Patients with AML rising from myelodysplasia may be included.

2) Into the expanded cohort at the MTD, previously untreated AML in patients over age 60 with poor- risk cytogenetics who are not eligible for or do not accept induction chemotherapy may also be included.

3) Signed informed consent form

Exclusion Criteria:1) Age less than 18 years

2) Eastern Cooperative Oncology Group (ECOG) performance status greater than 2

3) Active uncontrolled central nervous system leukemia

4) 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 longer. Hydroxyurea must be stopped at least 24 hours prior to the first dose of SAR103168.

5) Lack of recovery from toxicities from prior therapies to grade less than or equal to 1

6) WBC greater than 30 x 10(9)/L prior to the first dose of SAR103168

7) Prior allogeneic stem cell transplantation or donor lymphocytes infusion within 3 months preceding the first dose of SAR103168.

8) 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

9) Left Ventricular Ejection Fraction of less than 50% by dimensionally echocardiography or Multiple Gated Acquisition scan (MUGA) scan

10) Cardiac ischemia on 12-lead ECG (Will be evaluated and confirmed by a cardiologist): ST segment elevation or depression greater than 1 mm in at least 2 contiguous leads or presence of Qwaves

11) Baseline QTc interval greater than 500 msec

12) Hypertension uncontrolled with appropriate therapy (defined as systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg on two repeated measurements)

13) Active infection (viral, bacterial or fungal) uncontrolled with appropriate therapy

14) Major surgery within 6 weeks prior to the first dose of SAR103168

15) Any other serious active disease or co-morbid medical condition or laboratory abnormality, which may impair the ability to evaluate the drug safety or the compliance with the study

16) Poor organ function defined by one of the following: a. Total bilirubin > 1.5 x upper limit of normal (ULN) unless related to leukemia (i.e. hemolysis) or Gilbert's syndrome b. AST, ALT > 2.5 x ULN c. Serum creatinine > 1.5 x ULN or calculated creatinine clearance < 50 mL/min

17) 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

18) 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

19) Pregnant or breast-feeding women or refusal to use adequate contraceptive method, when applicable

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Links
Registration Number: NCT00981240
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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