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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

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ClinicalTrials.gov Identifier: NCT01534260
Recruitment Status : Completed
First Posted : February 16, 2012
Last Update Posted : March 30, 2018
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Bayer
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Hamid Sayar, Indiana University

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: sorafenib, vorinostat and bortezomib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : February 10, 2012
Actual Primary Completion Date : August 29, 2016
Actual Study Completion Date : February 13, 2017


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. Number of dose limiting toxicities (DLTs) after administration of sorafenib, vorinostat and bortezomib [ Time Frame: up to 9 months of treatment ]

Secondary Outcome Measures :
  1. 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 ]
  2. Duration to relapse in patients who experience relapse following achievement of a complete remission [ Time Frame: approximately 1 year after achieving complete remission ]
    This is defined as the duration of remission from the time of documentation of complete morphologic remission to the time of documentation of relapse.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01534260


Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Hamid Sayar
Millennium Pharmaceuticals, Inc.
Bayer
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Hamid Sayar, MD Indiana University Melvin and Bren Simon Cancer Center

Responsible Party: Hamid Sayar, Assistant Professor of Clinical Medicine, Indiana University
ClinicalTrials.gov Identifier: NCT01534260     History of Changes
Other Study ID Numbers: IUCRO-0327
1110007281 ( Other Identifier: Indiana University IRB )
First Posted: February 16, 2012    Key Record Dates
Last Update Posted: March 30, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Monosomy
Neoplasms by Histologic Type
Neoplasms
Aneuploidy
Chromosome Aberrations
Pathologic Processes
Sorafenib
Vorinostat
Bortezomib
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Histone Deacetylase Inhibitors