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TERMINATEDPHASE2

Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

Phase II Trial of Velcade Plus Vorinostat in the Treatment of High Risk MDS and Relapsed/Refractory AML

NCT00818649•Masonic Cancer Center, University of Minnesota

Summary

RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with vorinostat works in treating patients with high-risk myelodysplastic syndrome or acute myelogenous leukemia.

Detailed Description

OBJECTIVES: Primary * To determine the clinical response to bortezomib and vorinostat in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia, as defined by the International Working Group response criteria. Secondary * To characterize the quantitative and qualitative toxicities of this regimen in these patients. * To assess the effect of this regimen on natural killer (NK) cell function, in terms of activating and inhibitory receptor alterations, target cell ligand and HLA class I modulation, and NK-mediated cell killing. * To correlate the above changes with clinical response. OUTLINE: Patients receive bortezomib subcutaneously (SQ) on days 1, 4, 8, and 11 and oral vorinostat once daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response, partial response, or hematologic improvement may receive 3 additional courses of therapy (for a maximum of 6 courses). Bone marrow and peripheral blood samples are collected at baseline and at the completion of 3 courses of therapy for analysis of target cells (myeloid blasts) (i.e., HLA class I receptor analysis and natural killer \[NK\] cell receptor ligand analysis) and analysis of activating NK cell receptor alterations and NK-mediated cell killing. After completion of study treatment, patients are followed periodically for up to 1 year.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Disease Specific Criteria: Pathologic Diagnosis must be confirmed by University of Minnesota Hematopathology
•Myelodysplastic Syndrome (MDS): By IPSS Category: INT-2 or High risk, By WHO Classification: RAEB-1 or RAEB-2,By cytogenetics: High Risk Cytogenetic Abnormality Present as defined by the presence Monosomy 7 or complex karyotype. Patients will be eligible after progressing through standard therapy with either Azacitidine or Decitabine. Patients with a history of 5q minus syndrome may be eligible after progressing through treatment with Lenalidomide.
•Acute Myelogenous Leukemia (AML): Histologic subtypes M0,M1,M2,M4,M5,M6,M7 are eligible and must meet one of the three criteria below:
•* Refractory Disease/Induction Failure: Failure to achieve initial remission after 2 lines of induction therapy.
•* Relapsed Disease
•* Newly diagnosed/untreated AML: Patients who are not able to tolerate potentially curative conventional induction chemotherapy due to advanced age, end organ limitations, or performance status limitation will be eligible.
•Additionally, those that refuse conventional induction therapy will be eligible.
•Patients must have relatively stable bone marrow function during the week prior to enrollment on the study. White Blood cells (WBC) may be controlled with hydrea. Rapid WBC doubling not responsive to control with hydrea would indicate unstable bone marrow function. Ideally WBC should be \< 15 X 10\^3 /dl at time of study enrollment.
•Age \>18 years
•Karnofsky performance status \> or = 60%
+10 more criteria

Exclusion Criteria

•Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test within 72 hours prior to study drug administration to rule out pregnancy.
•Grade 2 or greater peripheral neuropathy within 14 days before enrollment
•Active central nervous system (CNS) disease. Patients with any clinical symptoms of active CNS disease must have LP with negative cytology.
•WBC and Peripheral Blast count uncontrolled with hydroxyurea
•Evidence of QT prolongation with QTc interval greater than 0.5 seconds. QTc calculation from the EKG machine will be used for this assessment.
•Clinical evidence of heart failure or history of uncontrolled hypertension. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
•Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies
•Patients with prior use of other histone deacetylase inhibitors (excluding valproic acid for seizures with a 30 day wash-out period)
•Known hypersensitivity to Velcade, boron or any of the other agents used in this study
•Patients with a history of deep vein thrombosis/pulmonary embolism (DVT/PE) that has not been adequately treated with systemic anticoagulation or that has been recently diagnosed (within the last 2 months).
+3 more criteria

Locations (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Key Dates

Start Date

January 1, 2009

Primary Completion Date

May 1, 2012

Completion Date

May 1, 2012

Last Updated

December 28, 2017

Enrollment

ACTUAL participants

Conditions

LeukemiaMyelodysplastic Syndrome

Interventions

bortezomib

DRUG

vorinostat

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: December 28, 2017Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

Inclusion Criteria

Exclusion Criteria

Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants

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