Granulocyte-colony Stimulating Factor (G-CSF) and Plerixafor Plus Sorafenib for Acute Myelogenous Leukemia (AML) With FLT3 Mutations - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborators:	Bayer Genzyme Onyx Pharmaceuticals
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00943943

Purpose

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.

Objectives:

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.

Condition	Intervention	Phase
Acute Myelogenous Leukemia Leukemia	Drug: G-CSF Drug: Plerixafor Drug: Sorafenib	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	G-CSF and Plerixafor With Sorafenib for Acute Myelogenous Leukemia With FLT3 Mutations

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA Help Me Understand Genetics

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Plerixafor Filgrastim Sargramostim Lenograstim Granulocyte colony-stimulating factor Sorafenib Sorafenib tosylate

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) Level [ Time Frame: Participant toxicity rates evaluated at 8 weeks of treatment (2 cycles) ] [ Designated as safety issue: Yes ]
MTD dose level where less than two participants (2/3) experience Dose limiting toxicity (DLT), based on NCI CTCAE v3.0, 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.

Estimated Enrollment:	28
Study Start Date:	October 2010
Estimated Primary Completion Date:	October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: G-CSF and Plerixafor with Sorafenib G-CSF 10 mcg/kg adjusted body weight subcutaneous injection. Plerixafor fixed dose of 240 mcg/kg adjusted body weight subcutaneous injection in abdomen. Patients will receive the 1st doses of G-CSF and Plerixafor on day 1. G-CSF and Plerixafor every other day for 7 total doses, repeated every 28 days. Sorafenib starting dose 400 mg twice daily orally after G-CSF/Plerixafor injections.	Drug: G-CSF 10 microgram/kg subcutaneous injection based on adjusted ideal body weight and administered in the evening (prior to the Plerixafor). The 1st dose on day -1 and every other day for 7 total doses. G-CSF administration of 7 every-other-day doses will be repeated every 28 days. Other Names: Granulocyte Colony Stimulating Factor Filgrastim Neupogen Drug: Plerixafor A fixed dose of 240 mcg/kg subcutaneous injection in the abdomen, calculated on ideal body weight. The 1st dose on day -1 and every other day for 7 total doses. Plerixafor administration of 7 every-other-day doses will be repeated every 28 days. Other Name: Mobozil Drug: Sorafenib First dose will be given right after G-CSF and plerixafor injections. Drug doses will be separated by intervals of approximately 12 hours (+/-2 hours). Dose Level 0 = 400 mg orally twice daily. Other Names: Nexavar BAY 43-9006

Arms

Assigned Interventions

Experimental: G-CSF and Plerixafor with Sorafenib

G-CSF 10 mcg/kg adjusted body weight subcutaneous injection. Plerixafor fixed dose of 240 mcg/kg adjusted body weight subcutaneous injection in abdomen. Patients will receive the 1st doses of G-CSF and Plerixafor on day 1. G-CSF and Plerixafor every other day for 7 total doses, repeated every 28 days. Sorafenib starting dose 400 mg twice daily orally after G-CSF/Plerixafor injections.

Drug: G-CSF

10 microgram/kg subcutaneous injection based on adjusted ideal body weight and administered in the evening (prior to the Plerixafor). The 1st dose on day -1 and every other day for 7 total doses. G-CSF administration of 7 every-other-day doses will be repeated every 28 days.

Other Names:

Granulocyte Colony Stimulating Factor
Filgrastim
Neupogen

Drug: Plerixafor

A fixed dose of 240 mcg/kg subcutaneous injection in the abdomen, calculated on ideal body weight. The 1st dose on day -1 and every other day for 7 total doses. Plerixafor administration of 7 every-other-day doses will be repeated every 28 days.

Other Name: Mobozil

Drug: Sorafenib

First dose will be given right after G-CSF and plerixafor injections. Drug doses will be separated by intervals of approximately 12 hours (+/-2 hours).

Dose Level 0 = 400 mg orally twice daily.

Other Names:

Nexavar
BAY 43-9006

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients will be 18 years of age or older.
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.
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
Able to take oral medication.
Able to understand and provide signed informed consent.
Ejection fraction at screening must be >/=50%.
Performance status < 3, unless directly related to leukemic disease process as determined by the Principal Investigator.

Exclusion Criteria:

Subjects with acute promyelocytic leukemia.
Patients with absolute blast count > 20 k/uL.
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.
Men not willing to maintain adequate contraception with their partner over the entire course of the study.
Hypertension > 140 mmHg systolic OR > 90 mmHg diastolic with or without antihypertensive therapy.
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.
Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients.
Known human immunodeficiency virus (HIV) infection or active Hepatitis B or C.
Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
Pulmonary hemorrhage/bleeding event >/= CTCAE Grade 2 within 4 weeks of first dose of study drug.
Any other hemorrhage/bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of study drug.
Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
Currently using St. John's Wort or rifampin.
Known or suspected allergy to sorafenib or any agent given in the course of this trial.
Active clinically serious and uncontrolled infection > CTCAE Grade 2.
Serious non-healing wound, ulcer, or bone fracture.
Patients currently receiving any other standard or investigational treatment for their hematologic malignancy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943943

Contacts

Contact: Michael Andreeff, MD, PhD

713-792-7260

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Michael Andreeff, MD, PhD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Bayer

Genzyme

Onyx Pharmaceuticals

Investigators

Principal Investigator:

Michael Andreeff, MD, PhD

M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00943943 History of Changes
Other Study ID Numbers:	2008-0501
Study First Received:	July 20, 2009
Last Updated:	February 2, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

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

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lenograstim
Sorafenib
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 23, 2012