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

NCT00981240 | Completed Phase 1

• 1 other identifier: TED10416
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of DLTs during the initial 4-week period of treatment

  4 weeks

• Pharmacokinetic parameters of SAR103168

  First course: Days 1, 2, 5, 6, and 8; Second and subsequent courses: Day 5 only

Secondary Outcomes (3)

• Global safety profile of SAR103168 based on treatment emergent adverse events (TEAEs), serious adverse events (SAEs), deaths, laboratory abnormalities

  Treatment period up to 1 year

• Preliminary evidence of anti-leukemia activity

  Treatment period up to 1 year

• Pharmacokinetic parameters of midazolam in the absence and the presence of SAR103168.

  During second (Day-1 and Day 5) and forth course (Day 5)

Study Arms (1)

Dose escalation

EXPERIMENTAL

Cohorts of 3 to 6 patients will be included at each dose level. The starting dose is 1.2mg/m2/day. The dose will be increased in new cohorts of patients according to toxicities observed during the first 4-week treatment period. The escalation process will continue until the MTD is determined. Additional 15 patients will be included at the MTD.

Drug: SAR103168

Interventions

SAR103168 DRUG

Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous infusion

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• Sanofi: lead

Study Sites (3)

Sanofi-Aventis Investigational Site Number 840003

Atlanta, Georgia, 30322, United States

Location

Sanofi-Aventis Investigational Site Number 840002

New York, New York, 10021, United States

Location

Sanofi-Aventis Investigational Site Number 840001

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Roboz GJ, Khoury HJ, Jabbour E, Session W, Ritchie EK, Miao H, Faderl S, Zheng W, Feldman EJ, Arellano M, Morrison JG, Ravandi F. Phase I trial of SAR103168, a novel multi-kinase inhibitor, in patients with refractory/relapsed acute leukemia or high-risk myelodysplastic syndrome. Leuk Lymphoma. 2015 Feb;56(2):395-400. doi: 10.3109/10428194.2014.918970.

  PMID: 24794806 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

SAR103168

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Farhad Ravandi-Kashani, MD

  M.D. Anderson Cancer Center, Houston, Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2009
• First Posted: September 22, 2009
• Study Start: September 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: February 1, 2012
• Last Updated: March 27, 2012

Record last verified: 2012-03

Locations

US (3)