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

NCT01075425 | Completed Phase 1 DMC

• 3 other identifiers: MCC-12517NCI-2010-00127RC2CA148431
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Lymphocytic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myelogenous Leukemia

Keywords

leukemia; acute leukemia; chronic myelogenous leukemia; myelodysplastic syndrome; relapsed acute leukemia; refractory acute leukemia; belinostat; bortezomib; Velcade; PXD-101

Outcome Measures

Primary Outcomes (1)

• Recommended phase II doses for the combination of bortezomib and belinostat

  2 years

Secondary Outcomes (3)

• Toxicity

  2 years

• Pharmacodynamic response

  2 years

• Activity of belinostat and bortezomib

  3 years

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Drug: bortezomib; Drug: belinostat; Other: laboratory biomarker analysis; Genetic: western blotting; Other: pharmacological study; Other: flow cytometry

Interventions

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, PS-341, VELCADE

Arm I

belinostat DRUG

Given IV

Also known as: PXD101

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Also known as: sample collection

Arm I

western blotting GENETIC

Correlative studies

Also known as: Blotting, Western, Western Blot

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

flow cytometry OTHER

Correlative studies

Also known as: sample analysis

Arm I

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory acute leukemia
• acute myeloid leukemia (AML) other than APL
• acute lymphocytic leukemia (ALL)
• acute leukemia that has evolved from a prior myelodysplastic syndrome - no requirement for prior therapy
• myelodysplastic Syndrome (MDS) - International Prognostic Scoring System (IPSS) intermediate-2 or greater
• chronic myelogenous leukemia with myeloid or lymphoid blast crisis
• WBC =\< 50 x 10\^9/L; hydroxyurea or leukopheresis may be used prior starting treatment
• Prior allogeneic stem cell transplant is allowed provided that \>/= 12 months have elapsed since allogeneic transplant; no graft versus host disease is present; not currently on immunosuppressive therapy
• AST, ALT =\< 2.5 x upper limit of normal (ULN)
• Female subject who is post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., oral or injectable hormonal methods; barrier methods such as intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
• Male subject agrees to use an acceptable method for contraception for the duration of the study
• Serum total bilirubin =\< 1.5 x upper limit of normal
• Serum potassium \>= 3.5 mEq/L and serum magnesium \>= 1.7 mEq/dL (electrolytes may be corrected with supplementation)
• ECOG Performance Status (PS) =\<2
• Creatinine =\< 1.5 x upper limit of normal or calculated or actual creatinine clearance \> 45 mL/min

You may not qualify if:

• Willing and medically suitable for remission induction with other agents in anticipation of a potentially curative allogeneic bone marrow transplant
• Known CNS malignant disease
• Prior severe allergic reactions to bortezomib, mannitol, boron, belinostat or compounds of the hydroxamate class or arginine
• Grade 1 with pain or Grade \>= 2 peripheral neuropathy or paresthesias within 14 days before enrollment
• History of sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, or resuscitated cardiac arrest
• History of resuscitated cardiac arrest. Note: persons without pre-existing cardiovascular comorbidities who have experienced resuscitated cardiac arrest in the setting of sepsis ARE eligible provided they have no residual cardiac abnormalities and providing they do not require ongoing medication to manage cardiac issues as an outcome of such an event.
• Conduction abnormality or concomitant treatment with an anti-arrhythmic agent to prevent or control arrhythmia
• Known congenital long QT syndrome
• Clinically significant infection including infection with HIV, or active hepatitis B or C
• Significant cardiovascular disease, hypertrophic cardiomegaly or restrictive cardiomyopathy, myocardial infarction within the past 6 months, unstable angina
• Baseline QTc interval \> 450 msec
• Planned or ongoing treatment with any drug that may be risk of causing Torsades de Pointes
• Persistent blood pressure (BP) of \>=160/95
• Serious medical or psychiatric illness likely to interfere with patient participation
• Pregnant or nursing

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Links

• VCU Massey Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia

Interventions

Bortezomib; belinostat; Specimen Handling; Blotting, Western; Flow Cytometry

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Cell Separation; Cytological Techniques; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry

Study Officials

• Steven Grant

  Virginia Commonwealth University

  STUDY CHAIR

• Beata Holkova, MD

  Massey 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 15, 2010
• First Posted: February 25, 2010
• Study Start: May 1, 2010
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: April 15, 2016

Record last verified: 2016-04

Locations

US (2)