Bortezomib, Sorafenib Tosylate, and Decitabine in Treating Patients With Acute Myeloid Leukemia

NCT01861314 | Active Not Recruiting Phase 1 DMC FDA Drug

• 8 other identifiers: NCI-2013-00999OSU-11186OSU 111869422P30CA016058R01CA158350U01CA076576UM1CA186712
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and the best dose of bortezomib and sorafenib tosylate when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bortezomib and sorafenib tosylate together with decitabine may work better in treating acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia; Acute Myeloid Leukemia Post Cytotoxic Therapy; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• BETD of bortezomib, sorafenib tosylate, and decitabine using National Cancer Institute Common Terminology Criteria for Adverse Events version 4

  Analysis will include summarization of the toxicity and tolerability by dose level. Frequency and severity of adverse events and tolerability of the regimen in each of the dose levels will be collected and summarized using descriptive statistics.

  28 days

Secondary Outcomes (2)

• CR rate

  Up to 30 days

• Change in miR-29b expression in blood and bone marrow

  Baseline to up to day 12 of course 1

Study Arms (1)

Treatment (bortezomib, sorafenib tosylate, decitabine)

EXPERIMENTAL

STEP A: Patients receive bortezomib SC on days 1 and 4, sorafenib tosylate PO BID on days 1-14, and decitabine IV over 1 hour on days 5-14. STEP B: Patients receive bortezomib SC on days 1, 4, and 8 or 1, 4, 8 and 11, sorafenib tosylate PO BID on days 1-14, and decitabine IV over 1 hour on days 9-18 or 12-21. STEP C: Patients receive bortezomib SC on days 1, 4, and 8 or 1, 4, 8 and 11, sorafenib tosylate PO BID on days 1-14, and decitabine IV over 1 hour on days 5-14. Treatment repeats every 28 days for up to 4 courses in the absence of unacceptable toxicity. Patients achieving CR or CRi receive maintenance therapy comprising decitabine IV on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sorafenib Tosylate

Interventions

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, LDP-341, LDP341, MLN 341, MLN-341, MLN341, PS 341, PS-341, PS341, Velcade

Treatment (bortezomib, sorafenib tosylate, decitabine)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (bortezomib, sorafenib tosylate, decitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (bortezomib, sorafenib tosylate, decitabine)

Sorafenib Tosylate DRUG

Given PO

Also known as: BAY 43-9006 Tosylate, BAY 54 9085, BAY 54-9085, BAY 549085, BAY-54-9085, BAY549085, Nexavar, sorafenib

Treatment (bortezomib, sorafenib tosylate, decitabine)

Pharmacological Study OTHER

Correlative studies

Treatment (bortezomib, sorafenib tosylate, decitabine)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML) by World Health Organization (WHO) criteria in the blood and/or marrow AND age \>= 60 and not candidates/refuse standard induction treatment OR who have one of the following: poor risk cytogenetics, AML following antecedent hematologic disorder, or therapy-related AML
• Patients with relapsed or refractory AML age \>= 18 years are also eligible for treatment; patients may have been treated for antecedent hematologic disorder with myeloid growth factors, recombinant erythropoietin, thalidomide, lenalidomide, 5-azacitidine or the 5 day schedule of decitabine; patients who have received the 10 day schedule of decitabine for treatment an antecedent hematologic disorder or AML are not eligible
• If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin \< 2.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transferase \[SGPT\]) \< 2.5 X institutional upper limit of normal
• Creatinine \< 2.0 mg/dL or creatinine clearance (CrCl) \>= 60 mL/min
• Prothrombin time (PT)/international normalized ratio (INR) monitoring, \< 1.5 x institutional upper limits of normal
• Both women and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; if the patient does not agree, the patient is not eligible
• Ability to understand and willingness to sign the written informed consent document

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; hydroxyurea may be administered for count control both pre-treatment and during cycle 1 only
• Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
• Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib, bortezomib or decitabine that are not easily managed
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; as infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Patients with pre-existing grade 2 or higher neuropathy or other serious neurologic toxicity that would significantly increase risk of complications from bortezomib therapy are excluded
• Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection who are taking chronic anti-retroviral therapy (HAART) are ineligible if there is a potential for drug-drug interactions with the chemotherapeutic agents; patients with a known confirmed diagnosis of HIV infection who meet standard eligibility criteria and are not taking HAART with a potential for drug-drug interactions are eligible
• Patients with advanced malignant solid tumors are excluded
• Patients with known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of sorafenib
• Patients who are taking concomitant medications that in the investigator's opinion are strong inducers of the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) enzymes and therefore likely to interact with the study agents, will not be eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Bortezomib; Decitabine; Injections; Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Alison R Walker

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2013
• First Posted: May 23, 2013
• Study Start: July 3, 2013
• Primary Completion: November 6, 2015
• Study Completion (Estimated): March 19, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (1)