- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01534260
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
July 20, 2018 updated by: Hamid Sayar
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
37
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University Melvin and Bren Simon Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: sorafenib, vorinostat and bortezomib
Escalating cohorts of 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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Dose Limiting Toxicity
Time Frame: up to 9 months
|
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
Time Frame: up to 9 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase II - Time to Relapse
Time Frame: Up to one year
|
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.
|
Up to one year
|
Phase II - Treatment-Related Adverse Events Grade 3 or Higher
Time Frame: Up to one year
|
Number of unique patients who had a treatment-related (possible, probable or definite) adverse events that were graded 3 or higher.
|
Up to one year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
February 10, 2012
Primary Completion (ACTUAL)
August 29, 2016
Study Completion (ACTUAL)
February 13, 2017
Study Registration Dates
First Submitted
February 13, 2012
First Submitted That Met QC Criteria
February 15, 2012
First Posted (ESTIMATE)
February 16, 2012
Study Record Updates
Last Update Posted (ACTUAL)
August 17, 2018
Last Update Submitted That Met QC Criteria
July 20, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Chromosome Aberrations
- Aneuploidy
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Monosomy
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Histone Deacetylase Inhibitors
- Sorafenib
- Bortezomib
- Vorinostat
Other Study ID Numbers
- IUCRO-0327
- 1110007281 (OTHER: Indiana University IRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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