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

NCT00875745 | Completed Phase 1 DMC

• 1 other identifier: 0902-08; IUCRO-0234
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose of a combination of Sorafenib and Vorinostat administered to patients with poor-risk AML, or MDS with >10% blasts.

  Baseline through cycle 3

Secondary Outcomes (2)

• Evaluate response and the duration of response to this combination targeted therapy

  Baseline through Cycle 3

• Evaluate the toxicity of the combination of Sorafenib and Vorinostat in patients receiving this therapy

  Baseline through Cycle 3

Study Arms (1)

Sorafenib-Vorinostat

EXPERIMENTAL

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

Interventions

Sorafenib-Vorinostat DRUG

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).

Also known as: Nexavar (Sorafenib), Zolinza (Vorinostat)

Sorafenib-Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University School of Medicine: lead
• Bayer: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes

Interventions

Sorafenib; Vorinostat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Anilides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Hamid Sayar, MD

  Indiana University Melvin and Bren Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2009
• First Posted: April 3, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: October 1, 2013
• Last Updated: September 18, 2014

Record last verified: 2014-09

Locations

US (1)