Clinical Trials /

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

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: IUCRO-0327
  • SECONDARY ID: 1110007281
  • NCT ID: NCT01534260

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
sorafenib, vorinostat and bortezomibsorafenib, vorinostat and bortezomib

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.

Trial Arms

NameTypeDescriptionInterventions
sorafenib, vorinostat and bortezomibExperimentalEscalating cohorts of sorafenib, vorinostat and bortezomib
  • sorafenib, vorinostat and bortezomib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients With Dose Limiting Toxicity
Time Frame:up to 9 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Phase II - Time to Relapse
Time Frame:Up to one year
Safety Issue:
Description:Will be examined using Kaplan-Meier estimates. Time from date of confirmed complete remission to date of relapse. The observations of patients who died or remained alive and relapse free were censored at date of death or last disease evaluation, respectively.
Measure:Phase II - Treatment-Related Adverse Events Grade 3 or Higher
Time Frame:Up to one year
Safety Issue:
Description:Number of unique patients who had a treatment-related (possible, probable or definite) adverse events that were graded 3 or higher.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Hamid Sayar

Last Updated