Phase I/II Study of Combination of Sorafenib, Vorinostat, and Bortezomib for the Treatment of Acute Myeloid Leukemia With Complex- or Poor-risk (Monosomy 5/7) Cytogenetics or FLT3-ITD Positive Genotype

NCT01534260 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IUCRO-03271110007281
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done because treatment options are very limited and usually unsuccessful for Acute Myeloid Leukemia (AML) in older individuals, or younger people with disease that has relapsed and/or proven resistant to standard therapy. Subjects are invited to participate in this study that will examine the use of three drugs called Sorafenib (Nexavar), Vorinostat (Zolinza) and Bortezomib (Velcade) for treating acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Dose Limiting Toxicity

  The number of patients who had a DLT during the dose finding/confirming portion (Phase I) of the trial for the safety of the combination of sorafenib, vorinostat, and bortezomib.

  up to 9 months

• Phase II - Percentage of Patients With a Partial Response or Greater

  Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better. The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the response criteria determined by the International Working Group for AML.

  up to 9 months

Secondary Outcomes (2)

• Phase II - Time to Relapse

  Up to one year

• Phase II - Treatment-Related Adverse Events Grade 3 or Higher

  Up to one year

Study Arms (1)

sorafenib, vorinostat and bortezomib

EXPERIMENTAL

Escalating cohorts of sorafenib, vorinostat and bortezomib

Drug: sorafenib, vorinostat and bortezomib

Interventions

sorafenib, vorinostat and bortezomib DRUG

Escalating dose cohorts of sorafenib, vorinostat and bortezomib. The first cohort will receive sorafenib from day 1 to 14, vorinostat will be given on days 1-4 and 8-12, and bortezomib will be given on days 1 and 8. This will be followed by 7 days of rest. Therefore each cycle will be 21 days.

sorafenib, vorinostat and bortezomib

Eligibility Criteria

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

You may qualify if:

• A confirmed baseline diagnosis of AML by the revised guidelines of the International Working Group for AML including newly diagnosed, relapsed or refractory disease.
• Poor-risk or complex cytogenetics profile, or deletion of chromosome 5, or deletion of chromosome 7, or positive FLT3-ITD mutation.
• The patient must have discontinued all previous therapies for acute leukemia for at least 14 days and recovered from the acute non-hematologic side effects of the therapy.
• Hydroxyurea to control peripheral blood blast count must be discontinued within 24 hours prior to the initiation of treatment.
• Patients must have an ECOG (Zubrod) performance status of 0-2
• Patients must have adequate hepatic and renal function according to the protocol within one week prior to treatment.
• Female patients must be postmenopausal, surgically sterile or agree to use effective methods of contraception throughout the study.
• Male patients, even if surgically sterilized, must agree to practice effective contraception throughout the study.
• Patients must be able to swallow and tolerate oral medications.

You may not qualify if:

• Known central nervous system (CNS) leukemia.
• Diagnosis of acute promyelocytic leukemia (APL).
• Grade \>/= 2 peripheral neuropathy.
• Serious illness including, significant ongoing or active infection, New York Heart Association (NYHA) Grade III or IV congestive heart failure, unstable angina or new onset angina or myocardial infarction within the past 6 months, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within past 3 months. Serious medical or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirements.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Active corneal erosions or history of abnormal corneal sensitivity test.
• Known or suspected history of severe hypersensitivity reaction to tyrosine kinase inhibitors, histone deacetylase inhibitors, proteosome inhibitors, boron, or mannitol.
• Female patients who are lactating or have a positive serum pregnancy test within 72 hours of initiation of treatment, or a positive urine pregnancy test on Day 1 before first dose of study drug.
• Concurrent use of other histone deacetylase inhibitors (e.g. valproic acid) are prohibited except for HDAC inhibitors or HDAC-inhibitor like agents used for non-cancer treatment (e.g. epilepsy), where a 14 day washout is allowed.
• Radiation therapy within 3 weeks before randomization.
• Patients with known HIV, or known active hepatitis B or C infections.

Sponsors & Collaborators

• Hamid Sayar: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Bayer: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Sorafenib; Vorinostat; Bortezomib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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; Anilides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Results Point of Contact

• Title: Dr. Hamid Sayar
• Organization: IndianaU

ssayar@iu.edu

(317) 948-7576

Study Officials

• Hamid Sayar, MD

  Indiana University Melvin and Bren Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: February 13, 2012
• First Posted: February 16, 2012
• Study Start: February 10, 2012
• Primary Completion: August 29, 2016
• Study Completion: February 13, 2017
• Last Updated: August 17, 2018
• Results First Posted: August 17, 2018

Record last verified: 2018-07

Locations

US (1)