G-CSF and Plerixafor with Sorafenib for acute myelogenous leukemia with FLT3 mutations
The goal of this clinical research study is to learn the most tolerable dose of Nexavarâ (sorafenib) when given in combination with Mobozilâ (plerixafor) and Neupogenâ (filgrastim) to patients with AML. The safety of this combination will also be studied.
Disease Group: Leukemia
Treatment Agent: G-CSF
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: No hospitalization is required for this study unless there are patient ;monitoring concerns.
Sponsor: Bayer HealthCare Pharmaceuticals, Inc.
Return Visit: Cycle 1 on day 1, 2, 3, 4, and 5 then weekly. Optional blood draws day 1 at 3 time points: hr 0, 5, and 12 and days 2, 4, and 14, and an optional extra research bone marrow aspiration both before treatment starts and on day 14-17.
Home Care: If agreeing to the optional research, presence is required, after the baseline ;visit, on days 1, 2, 4, and 14-17 for sample collections.
Primary: To determine the safety of Plerixafor and Filgrastim (G-CSF) in combination with sorafenib for treatment of refractory or relapsed myeloid leukemias with mutated fms-like tyrosine kinase receptor-3 (FLT3), and of elderly patients with acute myelogenous leukemia (AML) FLT3 mutations who are not eligible for frontline standard therapy, or who refuse to be treated with intensive chemotherapy. Secondary: Determine biologic effects of Plerixafor and G-CSF on leukemia cells in patients with refractory or relapsed myeloid leukemias with mutated FLT3.
IRB Review and Approval Date: 10/29/2010
Recruitment Status: Closed
Projected Accrual: N/A
1) Patients will be 18 years of age or older.
2) Patients must have relapsed/refractory leukemia with FLT3 (ITD) mutations. Patients with AML FLT3 mutations who are not eligible for frontline standard therapy, or who refuse to be treated with intensive chemotherapy, may be eligible.
3) Serum biochemical values with the following limits unless considered due to leukemia: creatinine </= 1.5 mg/dl; total bilirubin </= 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder; or transaminases (SGPT) </= 2.5 x ULN
4) Able to take oral medication.
5) Able to understand and provide signed informed consent.
6) Ejection fraction at screening must be >/=50%.
7) Performance status < 3, unless directly related to leukemic disease process as determined by the Principal Investigator.
1) Subjects with acute promyelocytic leukemia.
2) Patients with absolute blast count > 20 k/uL.
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) Men not willing to maintain adequate contraception with their partner over the entire course of the study.
5) Hypertension > 140 mmHg systolic OR > 90 mmHg diastolic with or without antihypertensive therapy.
6) 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.
7) Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients.
8) Known human immunodeficiency virus (HIV) infection or active Hepatitis B or C.
9) Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
10) Pulmonary hemorrhage/bleeding event >/= CTCAE Grade 2 within 4 weeks of first dose of study drug.
11) Any other hemorrhage/bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of study drug.
12) Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
13) Currently using St. John's Wort or rifampin.
14) Known or suspected allergy to sorafenib or any agent given in the course of this trial.
15) Active clinically serious and uncontrolled infection > CTCAE Grade 2.
16) Serious non-healing wound, ulcer, or bone fracture.
17) Patients currently receiving any other standard or investigational treatment for their hematologic malignancy.