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Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006)
This study is ongoing, but not recruiting participants.
First Received: October 10, 2007   Last Updated: January 26, 2010   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: Bayer
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00542971
  Purpose

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 Intervention Phase
AML
Acute Myeloid Leukemia
Myelodysplastic Disorders
Drug: Idarubicin
Drug: Sorafenib
Drug: Ara-C
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Phase I: Maximum Tolerated Dose (MTD) [ Time Frame: Twice a week for first two 28 day cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase II: Progression-Free Survival (PFS) Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 75
Study Start Date: October 2007
Estimated Study Completion Date: October 2011
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sorafenib + Idarubicin + Ara-C: Experimental Drug: Idarubicin
12 mg/m2 IV over 1 hour daily (days 1-3)
Drug: Sorafenib
400 mg for 7 days
Drug: Ara-C
1.5 g/m2 IV over 24 hours daily (days 1-4)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of 1) AML (WHO 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 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 2.5x 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 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 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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00542971

Locations
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
Bayer
Investigators
Principal Investigator: Farhad Ravandi-Kashani, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: The University of Texas M.D. Anderson Cancer Center ( Farhad Ravandi-Kashani, M.D./Associate Professor )
Study ID Numbers: 2006-0977
Study First Received: October 10, 2007
Last Updated: January 26, 2010
ClinicalTrials.gov Identifier: NCT00542971     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
AML
High-Risk MDS
Acute Myeloid Leukemia
High-Risk Myelodysplastic Disorder
Idarubicin
Ara-C
Cytarabine
Sorafenib
BAY43-9006

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Disease
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Leukemia, Myeloid
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Protein Kinase Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Leukemia
Neoplasms
Idarubicin
Pathologic Processes
Therapeutic Uses
Sorafenib
Cytarabine

ClinicalTrials.gov processed this record on February 04, 2010