Combination of Sorafenib and Vorinostat in Poor-risk Acute Myelogenous Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS) - Full Text View

Sponsor:	Indiana University School of Medicine
Collaborator:	Bayer
Information provided by:	Indiana University
ClinicalTrials.gov Identifier:	NCT00875745

Purpose

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.

Condition	Intervention	Phase
Leukemia, Myeloid, Acute Leukemia, Promyelocytic, Acute Myelodysplastic Syndromes	Drug: Sorafenib-Vorinostat	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

Genetics Home Reference related topics: acute promyelocytic leukemia

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia Myelodysplastic Syndromes

Drug Information available for: Suberoylanilide hydroxamic acid Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Indiana University:

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. [ Time Frame: Baseline through cycle 3 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate response and the duration of response to this combination targeted therapy [ Time Frame: Baseline through Cycle 3 ] [ Designated as safety issue: No ]
Evaluate the toxicity of the combination of Sorafenib and Vorinostat in patients receiving this therapy [ Time Frame: Baseline through Cycle 3 ] [ Designated as safety issue: Yes ]

Enrollment:	15
Study Start Date:	April 2009
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sorafenib-Vorinostat This is a single-arm, non-randomized feasibility and safety Phase I trial of a combination of Sorafenib and Vorinostat, both administered orally.	Drug: Sorafenib-Vorinostat 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). Other Names: Nexavar (Sorafenib) Zolinza (Vorinostat)

Eligibility

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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00875745

Locations

United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University School of Medicine

Bayer

Investigators

Principal Investigator:

Hamid Sayar, MD

Indiana University Melvin and Bren Simon Cancer Center

More Information

No publications provided

Responsible Party:	Hamid Sayar, MD/ Principal Investigator, Indiana University Melvin and Bren Simon Cancer Center
ClinicalTrials.gov Identifier:	NCT00875745 History of Changes
Other Study ID Numbers:	0902-08; IUCRO-0234
Study First Received:	April 2, 2009
Last Updated:	July 29, 2010
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Promyelocytic, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases

Precancerous Conditions
Vorinostat
Sorafenib
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012