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G-CSF and Plerixafor With Sorafenib for Acute Myelogenous Leukemia With FLT3 Mutations


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Acute Myelogenous Leukemia, Leukemia

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Trial Information

G-CSF and Plerixafor With Sorafenib for Acute Myelogenous Leukemia With FLT3 Mutations


The Study Drugs:

Sorafenib is a type of drug called a multikinase inhibitor. It is designed to interfere with
the parts of cancer cells that are involved in the sending of chemical messages and helping
the cells divide and grow, which may block the formation of tumors and cause cell death.

Filgrastim promotes the growth of white blood cells, which help to fight infections.

Plerixafor is designed to help move stem cells from the bone marrow to the blood.

Study Drug Dose Level:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level and schedule of sorafenib based on when you joined this study. Up to 5 dose levels
and schedules will be tested. Three (3) participants will be enrolled at each dose level for
Phase I of the study. The first group of participants will receive dose level "0" of
sorafenib. If unacceptable side effects are seen, a dose lower than level "0" will be tried.
If no side effects are seen, the next group of 3 patients will be placed on a higher dose
level, called Level "1." Each new group will either receive a higher or lower dose of
sorafenib or take it more or less often than the group before it, based on whether
intolerable side effects are seen. This will continue until the best tolerable dose and
schedule of sorafenib is found. Once the best tolerable dose and/or schedule is found, the
last 10 participants will be enrolled and will take sorafenib at that dose and schedule.
This last group of 10 is considered the early Phase II part of the study.

Each group will receive the same dose level and schedule of filgrastim and plerixafor.

Study Drug Administration:

You will receive filgrastim and plerixafor by injection through a needle under the skin on
Day 1 (the day the study starts) and then every other day for a total of 7 doses. The
injections will be given in the morning. After day one, the injections may be done at your
home. Your study doctor will meet with you one-on-one to discuss how the drug will be
given.

On Day 1, you will begin taking your dose of sorafenib by mouth every other day, once a day,
or twice a day, depending on when you join the study.

- If you are taking sorafenib every other day, during Cycle 1 you will start taking it 12
hours after the filgrastim and plerixafor injections (the next morning).

- If you are taking sorafenib every day, you will take it at the same time every morning.
The first time you take sorafenib during Cycle 1 will be 12 hours after the first
filgrastim and plerixafor injections.

- If you are taking sorafenib twice a day, during Cycle 1 you will start taking it 12
hours after the filgrastim and plerixafor injections and then every 12 hours.

You will take sorafenib without food, at least 1 hour before or 2 hours after eating. If you
miss a dose, do not take double the dose next time to make up for the missed dose.

These 28 days are one "study cycle".

You are allowed to take hydroxyurea or other treatments to control high white blood cell
counts.

Study Drug Diary:

You will be given a study drug diary that you will be expected to fill out whenever you take
study drugs at home. A staff member will explain to you how to fill out the diary. The study
staff will review the diary with you at every study visit and you will be given a new diary
at the beginning of every cycle you start.

Study Visits:

Every week for the first 6 weeks and then every 4-8 weeks, the following tests and
procedures will be performed:

- You will have a physical exam, including measurement of your weight, and vital signs.

- You will have a bone marrow aspiration and biopsy done before treatment starts and once
somewhere between day 14 and day 17 after the first Sorafenib administration. Another
bone marrow sample will be collected between days 24 and 28.

- If you continue on study, another bone marrow sample will be collected after the third
cycle.

- Blood (about 1 teaspoon) will be drawn every 2-4 days for routine tests while you are
taking the study drugs and once a week on days you are not taking the study drugs
Plerixafor and Neupogen.

- During the first week, blood (about 1 teaspoon) will be drawn to check the status of
the disease before each dose of the filgrastim and plerixafor combination and again 4
to 8 hours after receiving the study drugs. If your doctor feels it is needed,
additional blood may be drawn after the 2nd blood draw to check the status of the
disease. If your doctor feels it is needed, these blood draws may continue after the
first week if the disease is not responding.

Length of Study:

You may continue taking the study drugs for up to 6 cycles (about 6 months). If you are in
complete remission, partial remission, or complete remission with incomplete platelet count
recovery after 6 months with no intolerable side effects, your doctor may discuss continuing
on the study with you. You will be taken off study if the disease gets worse or intolerable
side effects occur.

End-of-Study Visit:

You will have an end-of-study visit about 30 days after your last dose of the study drugs.
At this visit, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You will have a bone marrow aspirate and biopsy to check the status of the disease.

This is an investigational study. Sorafenib is FDA-approved and commercially available for
treatment of advanced renal cell cancer (RCC) and hepatocellular cancer (HCC) that cannot be
removed by surgery. Its use in patients with AML is investigational.

Plerixafor is FDA-approved and commercially available for use in boosting the number of
hematopoietic stem cells (HSC) for stem cell collection and transplants (in combination with
filgrastim) in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Its use
in patients with AML is investigational.

Filgrastim (NeupogenÒ) is FDA-approved and commercially available for use in boosting white
blood cell production in patients with low blood cell counts caused by chemotherapy
(nonmyeloid malignancies, acute myeloid leukemia, and bone marrow transplantation), treating
severe chronic neutropenia (SCN-low blood counts), and boosting production of hematopoietic
progenitor cells in patients undergoing peripheral blood progenitor cell (PBPC) collection.

Up to 28 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



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 hemolysis or congenital disorder; or transaminases (SGPT)
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.

Exclusion Criteria:

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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) Level

Outcome Description:

MTD dose level where less than two participants (2/3) experience Dose limiting toxicity (DLT), based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, is defined as ± Grade 3 nonhematological toxicity or nausea/vomiting (in the absence of appropriate antiemetics) that cannot be explained by intercurrent conditions such as infections and at least possibly related to the combination of agents in study.

Outcome Time Frame:

Participant toxicity rates evaluated at 8 weeks of treatment (2 cycles)

Safety Issue:

Yes

Principal Investigator

Michael Andreeff, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2008-0501

NCT ID:

NCT00943943

Start Date:

October 2010

Completion Date:

Related Keywords:

  • Acute Myelogenous Leukemia
  • Leukemia
  • acute myelogenous leukemia
  • AML
  • Leukemia
  • myeloid leukemias
  • mutated fms-like tyrosine kinase receptor-3
  • FLT3 Mutations
  • G-CSF
  • Granulocyte Colony Stimulating Factor
  • Filgrastim
  • Neupogen
  • Plerixafor
  • Mobozil
  • Sorafenib
  • BAY 43-9006
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

UT MD Anderson Cancer Center Houston, Texas  77030