Belinostat and Bortezomib in Treating Patients With Relapsed or Refractory Acute Leukemia or Myelodysplastic Syndrome

Phase 1

Completed

• Conditions: Acute Lymphocytic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myelogenous Leukemia
• Interventions: Drug: bortezomib; Drug: belinostat; Other: laboratory biomarker analysis; Genetic: western blotting; Other: pharmacological study; Other: flow cytometry

• Registration Number: NCT01075425
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

RATIONALE: Belinostat and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving belinostat together with bortezomib may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of giving belinostat together with bortezomib in treating patients with relapsed or refractory acute leukemia or myelodysplastic syndrome.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the recommended phase II doses for the combination of bortezomib and belinostat in patients with relapsed or refractory acute leukemia (AL), myelodysplasia (MDS), and chronic myelogenous leukemia in blast crisis. SECONDARY OBJECTIVES: I. Determine safety and tolerance and describe the toxicities of the combination. II. To demonstrate adequate methods for the assessment of pharmacodynamic response of leukemia cells from the bone marrow and/or peripheral blood in terms of effects on NF-kB (nuclear RelA by immunofluorescence microscopy), NF-kB dependent proteins XIAP and Bcl-xL, and BIM, and document pharmacodynamic responses observed in the course of this study. III. To document activity of the combination observed in the course of this study. OUTLINE: Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Study Timeline

• Study First Submitted: 2010-02-15
• Study First Submitted QC: 2010-02-23
• Study First Posted: 2010-02-25
• Study Start: 2010-05
• Primary Completion: 2015-02
• Study Completion: 2015-02
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-13
• Last Update Posted: 2016-04-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm I	western blotting	Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm I	pharmacological study	Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm I	flow cytometry	Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm I	belinostat	Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Arm I	bortezomib	Patients receive belinostat IV over 30 minutes on days 1-5 and 8-12 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Recommended phase II doses for the combination of bortezomib and belinostat	2 years

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic response	2 years
Toxicity	2 years
Activity of belinostat and bortezomib	3 years

Trial Locations

Locations (2)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States