Azacytidine and Bortezomib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes

• Status: Completed
• Trial end date: 2014-06-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as azacytidine work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. Giving azacytidine together with bortezomib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when giving together with azacytidine in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: Celgene Corporation; Millennium Pharmaceuticals, Inc.; National Cancer Institute (NCI)
• Treatments: Azacitidine; Bortezomib

Criteria

Inclusion criteria:

• Patients must be >18 with relapsed or refractory acute myeloid leukemia (AML) and high risk (by IPSS scoring) Myelodysplastic Syndromes (MDS)

• Patients with secondary AML or therapy related disease (t-AML) are eligible If decitabine or Vidaza was a prior treatment for MDS or AML patient is eligible.Prior Velcade is also permitted.

• ECOG performance status 0-2

• Life expectancy > 6 months for patients with a co-morbid medical illness

• Total bilirubin < 2.0mg/dL

• AST/ALT < 2.5 times upper limit of normal (ULN)

• Creatinine < 2.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception prior to and during study treatment

• Ability to understand and willingness to sign the written informed consent document

• Active infection is allowed provided it is under control

Exclusion criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacytidine or bortezomib that are not easily managed

• Hypersensitivity to bortezomib, boron, or mannitol

• Uncontrolled intercurrent illness including, but not limited to:

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Serious cardiac arrhythmia

• Psychiatric illness/social situations that would limit compliance with study

• Myocardial infarction within 6 months prior to enrollment

• New York Heart Association (NYHA) Class III or IV congestive heart failure

• Uncontrolled angina

• Severe uncontrolled ventricular arrhythmia

• Electrocardiographic evidence of acute ischemia

• Active conduction system abnormalities

• ECG abnormality that is medically relevant

• Psychiatric conditions that prevent compliance with protocol or consent.

• Pre-existing neuropathy grade 2 or higher or other serious neurologic toxicity that would significantly increase risk of complications from bevacizumab therapy

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study

• Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of any of the following:

• Complete resected basal cell carcinoma

• Squamous cell carcinoma of the skin

• Any in situ malignancy

• Low-risk prostate cancer after curative therapy

PRIOR CONCURRENT THERAPY:

• Prior decitabine or azacytidine for MDS or AML is allowed

• Prior bortezomib allowed

• More than 2 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)

• More than 14 days since prior and no concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients