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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Indiana University
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Bayer
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01534260
First received: February 13, 2012
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: sorafenib, vorinostat and bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Number of dose limiting toxicities (DLTs) after administration of sorafenib, vorinostat and bortezomib [ Time Frame: up to 9 months of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of patients with a partial response or greater to the combination of sorafenib, vorinostat and bortezomib [ Time Frame: up to 9 months of treatment ] [ Designated as safety issue: No ]
  • Duration to relapse in patients who experience relapse following achievement of a complete remission [ Time Frame: approximately 1 year after achieving complete remission ] [ Designated as safety issue: No ]
    This is defined as the duration of remission from the time of documentation of complete morphologic remission to the time of documentation of relapse.


Estimated Enrollment: 38
Study Start Date: February 2012
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sorafenib, vorinostat and bortezomib
Escalating cohorts of sorafenib, vorinostat and bortezomib
Drug: sorafenib, vorinostat and bortezomib
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.

  Eligibility

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534260

Contacts
Contact: Mary Cangany, RN 317-274-2178 mcangany@iupui.edu
Contact: Hamid Sayar, MD 317-944-7126 ssayar@iupui.edu

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Mary Cangany, RN    317-274-2178    mcangany@iupui.edu   
Contact: Hamid Sayar, MD    317-944-7126    ssayar@iupui.edu   
Principal Investigator: Hamid Sayar, MD         
Sponsors and Collaborators
Indiana University
Millennium Pharmaceuticals, Inc.
Bayer
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Hamid Sayar, MD Indiana University Melvin and Bren Simon Cancer Center
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01534260     History of Changes
Other Study ID Numbers: 1110007281; IUCRO-0327
Study First Received: February 13, 2012
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Sorafenib
Bortezomib
Vorinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014