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

NCT00624936 | Completed Phase 1 DMC

• 2 other identifiers: OSU-07095NCI-2011-03146
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); recurrent adult acute myeloid leukemia; myelodysplastic/myeloproliferative neoplasm, unclassifiable; myelodysplastic syndromes; secondary acute myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of bortezomib in combination with azacytidine

  Determine the maximum tolerated dose (MTD) of Velcade (bortezomib, PS-341) in combination with Vidaza in patients with relapsed/refractory acute myeloid leukemia (AML) and Myelodysplastic Syndrome (MDS)

  Up to 1 year

• Overall response rate

  Determine the overall response rate (ORR)

  Up to 1 year

Secondary Outcomes (5)

• Rate of complete remission

  Up to 1 year

• Biological activity of azacytidine and bortezomib as demethylating agents

  Up to 1 year

• Correlation of intracellular concentration of azacytidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response

  Up to 1 year

• Biologic role of microRNAs in determining clinical response to study drugs

  Up to 1 year

• Achievement of other pharmacodynamic endpoints

  Up to 1 year

Study Arms (1)

Vidaza and Velcade

EXPERIMENTAL

Vidaza 75mg/m2 IV over 30 min daily on days 1-7 This dose is the same for all dose levels. Velcade will be given immediately after Vidaza is completed at one of the following dose levels: 1, 2, 3, 4

Drug: Vidaza; Drug: Velcade

Interventions

Vidaza DRUG

Vidaza 75mg/m2 IV over 30min daily on days 1-7. This dose is the same for all dose levels.

Also known as: Azacitidina, Azacitidinum, Azacytidine, Mylosar

Vidaza and Velcade

Velcade DRUG

Dose level 1 Velcade 0.7mg/m2 IVP on days 2 and 5 Dose level 2 Velcade 0.7mg/m2 IVP on days 2, 5, 9, 12 Dose level 3 Velcade 1.0 mg/m2 IVP on days 2, 5, 9, 12 Dose level 4 Velcade 1.3 mg/m2 IVP on days 2, 5, 9, 12

Also known as: Bortezomib

Vidaza and Velcade

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Jamesline

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Congenital Abnormalities; Leukemia, Myeloid, Acute; Myeloproliferative Disorders

Interventions

Azacitidine; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Study Officials

• William G. Blum, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Guido Marcucci, MD

  Ohio State University Comprehensive 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: February 27, 2008
• First Posted: February 28, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: June 1, 2014
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

US (1)