Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00542971
Recruitment Status : Completed
First Posted : October 12, 2007
Results First Posted : July 13, 2012
Last Update Posted : July 13, 2012
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

A primary goal of this clinical research study is to find the highest safe dose of sorafenib that can be given in combination with idarubicin and Ara-C for the treatment of acute myelogenous leukemia (AML) and high-risk, myelodysplastic syndrome (MDS).

Once the highest safe dose is found, researchers will then try to learn if this combination treatment can help control AML and high-risk MDS in newly diagnosed patients. The safety of this treatment combination will also be studied.

Condition or disease Intervention/treatment Phase
AML Acute Myeloid Leukemia Myelodysplastic Disorders Drug: Idarubicin Drug: Sorafenib Drug: Ara-C Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006), an Oral VEGF, RAF and FLT3 Inhibitor, in Patients With High-risk MDS and AML
Study Start Date : October 2007
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011

Arm Intervention/treatment
Experimental: Sorafenib + Idarubicin + Ara-C
Sorafenib starting dose 400 mg orally for 7 days; Idarubicin 12 mg/m2 intravenous (IV) daily (days 1-3); and Ara-C 1.5 g/m2 IV over 24 hours daily (days 1-4)
Drug: Idarubicin
12 mg/m2 IV over 1 hour daily (days 1-3)
Other Name: Idamycin®, Idamycin PFS®
Drug: Sorafenib
Starting dose 400 mg by mouth for 7 days
Other Name: Nexavar®
Drug: Ara-C
1.5 g/m2 IV over 24 hours daily (days 1-4)
Other Names:
  • Cytarabine
  • Cytosar-U®
  • Arabinosylcytosine

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: Twice a week for first two 28 day cycles ]
    MTD is dose level where grade 3-4 sorafenib-attributable toxicity in <2 of 6 participants. Dose-Limiting Toxicity graded according to the NCI Common Toxicity Criteria version 3.0.

Secondary Outcome Measures :
  1. Number of Participants With Complete Response [ Time Frame: Baseline to 2 years or disease progression. ]
    Complete response was defined by the presence of < 5% blasts in the bone marrow (BM) with > 1 x 10^9/L platelets in the peripheral blood (PB).

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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of 1) AML (World Health Organization classification definition of > 20% blasts), or 2) high risk MDS (defined as the presence of > 10% blasts).
  2. Patients aged 15 to 60 years are eligible. Patients older than 60 who are deemed fit to receive intensive chemotherapy by the treating physician are eligible after discussion with the Principal Investigator (PI). For the Phase II portion of the study, patients must be chemo-naïve, i.e. not have received any prior chemotherapy (except hydrea) for AML or MDS. They could have received hypomethylator agents, transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as pheresis or hydrea are allowed. In the Phase I portion, patients with relapsed or refractory AML/MDS are also eligible.
  3. Serum biochemical values with the following limits unless considered due to leukemia: 1) creatinine less than or equal to 2 mg/dl, 2) total bilirubin less than or equal to 2 mg/dL, unless increase is due to hemolysis or congenital disorder, and 3) transaminases (SG PT) less than or equal to 2.5 times ULN
  4. Ability to take oral medication.
  5. Ability to understand and provide signed informed consent.
  6. Baseline test of ejection fraction must be >/=50%.
  7. Performance status < 3, unless directly related to the disease process as determined by the principal investigator.

Exclusion Criteria:

  1. Patients with Acute promyelocytic leukemia (APL).
  2. Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results.
  3. Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study.
  4. Any significant, uncontrolled hypertension.
  5. Cardiac disease: Congestive heart failure > class II The New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  6. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients.
  7. Known human immunodeficiency virus (HIV) infection or active Hepatitis B or C.
  8. Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  9. Pulmonary hemorrhage/bleeding event > or = to Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug.
  10. Any other hemorrhage/bleeding event > or = to CTCAE Grade 3 within 4 weeks of first dose of study drug.
  11. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  12. Use of St. John's Wort or rifampin.
  13. Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  14. Active clinically serious and uncontrolled infection > CTCAE Grade 2
  15. Serious non-healing wound, ulcer, or bone fracture

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00542971

United States, Texas
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Farhad Ravandi-Kashani, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00542971     History of Changes
Other Study ID Numbers: 2006-0977
First Posted: October 12, 2007    Key Record Dates
Results First Posted: July 13, 2012
Last Update Posted: July 13, 2012
Last Verified: June 2012

Keywords provided by M.D. Anderson Cancer Center:
High-Risk MDS
Acute Myeloid Leukemia
High-Risk Myelodysplastic Disorder

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors