Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
Primary Purpose
Leukemia, Myeloid, Acute, Leukemia, Promyelocytic, Acute, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sorafenib-Vorinostat
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
Eligibility Criteria
Inclusion Criteria:
- Patients must have a diagnosis of AML (> 20% myeloid blasts in the peripheral blood or bone marrow) or MDS with > 10% myeloid blasts in the bone marrow. Patients with Acute Promyelocytic Leukemia (APL) must be refractory to all-trans retinoic acid (ATRA) and arsenic trioxide.
The patients must have one of the following criteria:
- Age of 18 to 69 years; relapsed or refractory disease following at least one prior therapeutic regimen; not a candidate for cytotoxic or other conventional therapies due to disease refractoriness, poor performance status, or co-morbidities
- Age of 70 years or older; received no previous therapies (other than hematopoietic growth factors or hydroxyurea); not a candidate for cytotoxic or other conventional therapies due to poor performance status, co-morbidities, or personal preference
- Age of 70 years or older with relapsed or refractory disease
- The patient must have discontinued all previous therapies for acute leukemia for at least 14 days and recovered from the acute effects of the therapy.
- Patients must have an ECOG (Zubrod) performance status of 0-2
- Patients must be able to take and tolerate oral medications
- Patients must have adequate organ function as specified in the protocol.
- Patients not on anti-coagulation must have an INR < 1.5 and a PTT within normal limits.
Exclusion Criteria:
- Pregnant women or nursing mothers are not eligible for this trial.
- Patients may receive no other concurrent biologic therapy, cytotoxic chemotherapy or radiation therapy during this trial.
- Patients with one or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study. See protocol for listing.
- Patients with known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging
- Patients with previous autologous or allogeneic stem cell transplantation who have current side effects and/or complications that in the opinion of the investigator can interfere with the interpretation of the toxicities.
Sites / Locations
- Indiana University Melvin and Bren Simon Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sorafenib-Vorinostat
Arm Description
This is a single-arm, non-randomized feasibility and safety Phase I trial of a combination of Sorafenib and Vorinostat, both administered orally.
Outcomes
Primary Outcome Measures
Determine the maximum tolerated dose of a combination of Sorafenib and Vorinostat administered to patients with poor-risk AML, or MDS with >10% blasts.
Secondary Outcome Measures
Evaluate response and the duration of response to this combination targeted therapy
Evaluate the toxicity of the combination of Sorafenib and Vorinostat in patients receiving this therapy
Full Information
NCT ID
NCT00875745
First Posted
April 2, 2009
Last Updated
September 17, 2014
Sponsor
Indiana University School of Medicine
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00875745
Brief Title
Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
Official Title
Phase I, Open-label, Dose-escalation Study of the Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University School of Medicine
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to test the safety of sorafenib and vorinostat when given together to see what effects (good and bad) it has on the patient and their acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). This study is also being done to find the highest dose of sorafenib and vorinostat that can be given together without causing severe side effects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, Leukemia, Promyelocytic, Acute, Myelodysplastic Syndromes
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sorafenib-Vorinostat
Arm Type
Experimental
Arm Description
This is a single-arm, non-randomized feasibility and safety Phase I trial of a combination of Sorafenib and Vorinostat, both administered orally.
Intervention Type
Drug
Intervention Name(s)
Sorafenib-Vorinostat
Other Intervention Name(s)
Nexavar (Sorafenib), Zolinza (Vorinostat)
Intervention Description
Patients will be entered in successive cohorts. The first cohort will receive Sorafenib at 400 mg bid (800 mg daily) and Vorinostat at 100 mg bid (200 mg daily).
Primary Outcome Measure Information:
Title
Determine the maximum tolerated dose of a combination of Sorafenib and Vorinostat administered to patients with poor-risk AML, or MDS with >10% blasts.
Time Frame
Baseline through cycle 3
Secondary Outcome Measure Information:
Title
Evaluate response and the duration of response to this combination targeted therapy
Time Frame
Baseline through Cycle 3
Title
Evaluate the toxicity of the combination of Sorafenib and Vorinostat in patients receiving this therapy
Time Frame
Baseline through Cycle 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have a diagnosis of AML (> 20% myeloid blasts in the peripheral blood or bone marrow) or MDS with > 10% myeloid blasts in the bone marrow. Patients with Acute Promyelocytic Leukemia (APL) must be refractory to all-trans retinoic acid (ATRA) and arsenic trioxide.
The patients must have one of the following criteria:
Age of 18 to 69 years; relapsed or refractory disease following at least one prior therapeutic regimen; not a candidate for cytotoxic or other conventional therapies due to disease refractoriness, poor performance status, or co-morbidities
Age of 70 years or older; received no previous therapies (other than hematopoietic growth factors or hydroxyurea); not a candidate for cytotoxic or other conventional therapies due to poor performance status, co-morbidities, or personal preference
Age of 70 years or older with relapsed or refractory disease
The patient must have discontinued all previous therapies for acute leukemia for at least 14 days and recovered from the acute effects of the therapy.
Patients must have an ECOG (Zubrod) performance status of 0-2
Patients must be able to take and tolerate oral medications
Patients must have adequate organ function as specified in the protocol.
Patients not on anti-coagulation must have an INR < 1.5 and a PTT within normal limits.
Exclusion Criteria:
Pregnant women or nursing mothers are not eligible for this trial.
Patients may receive no other concurrent biologic therapy, cytotoxic chemotherapy or radiation therapy during this trial.
Patients with one or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study. See protocol for listing.
Patients with known central nervous system (CNS) leukemia by spinal fluid cytology, flow cytometry or imaging
Patients with previous autologous or allogeneic stem cell transplantation who have current side effects and/or complications that in the opinion of the investigator can interfere with the interpretation of the toxicities.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hamid Sayar, MD
Organizational Affiliation
Indiana University Melvin and Bren Simon Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Melvin and Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
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