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

NCT00943943 | Completed Phase 1 FDA Drug

• 4 other identifiers: 2008-0501R01FD003733R21CA143805NCI-2009-01512
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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. Funding Source - FDA OOPD

Conditions

Acute Myelogenous Leukemia; Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Sorafenib

  MTD dose level of Sorafenib 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.

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

Study Arms (1)

G-CSF and Plerixafor with Sorafenib

EXPERIMENTAL

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; Drug: Plerixafor; Drug: Sorafenib

Interventions

G-CSF DRUG

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.

Also known as: Granulocyte Colony Stimulating Factor, Filgrastim, Neupogen

G-CSF and Plerixafor with Sorafenib

Plerixafor DRUG

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.

Also known as: Mobozil

G-CSF and Plerixafor with Sorafenib

Sorafenib DRUG

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.

Also known as: Nexavar, BAY 43-9006

G-CSF and Plerixafor with Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 upper limit of normal (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.

You may not qualify if:

• 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, intrauterine device (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 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator
• Genzyme, a Sanofi Company: collaborator
• Amgen: collaborator
• National Cancer Institute (NCI): collaborator
• Georgia Institute of Technology: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Leukemia, Myeloid

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; plerixafor; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Michael Andreeff, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2009
• First Posted: July 22, 2009
• Study Start: October 29, 2010
• Primary Completion: March 23, 2017
• Study Completion: March 23, 2017
• Last Updated: March 29, 2017

Record last verified: 2017-03

Locations

US (1)