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Acute Lymphocytic LeukemiaPhase 1NCT01075425

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

A Phase 1 study testing bortezomib, belinostat and laboratory biomarker analysis in people with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia, run by Virginia Commonwealth University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bortezomib, belinostat and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesUnited States
Study dates
May 2010to Feb 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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
  • Diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy
  • Planned ongoing treatment with other drugs thought to potentially adversely interact with belinostat
  • Strong or moderate CYP3A4 inhibitors
  • Patient has received other investigational drugs within 14 days before enrollment
  • If steroids for cancer control have been used, patients must be off these agents for >/= 1 week before starting treatment. Exception: maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose < 10 mg/day is permitted.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: Phase I Study of Belinostat (PXD-101) and Velcade (Bortezomib) in Relapsed or Refractory Acute Leukemia/ Myelodysplastic Syndrome

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.

Read the 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.

Being tested
bortezomib, belinostat, laboratory biomarker analysis, western blotting, pharmacological study
Keywords
leukemia, acute leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, relapsed acute leukemia, refractory acute leukemia, belinostat, bortezomib, Velcade, PXD-101
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bortezomibDrug

    Also called LDP 341, MLN341, PS-341, VELCADE

    Given IV

  • belinostatDrug

    Also called PXD101

    Given IV

  • laboratory biomarker analysisOther

    Also called sample collection

    Correlative studies

  • western blottingGenetic

    Also called Blotting, Western, Western Blot

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • flow cytometryOther

    Also called sample analysis

    Correlative studies

Study groups in NCT01075425
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: bortezomib; Drug: belinostat; Other: laboratory biomarker analysis; Genetic: western blotting; Other: pharmacological study; Other: flow cytometry

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended phase II doses for the combination of bortezomib and belinostat

    Measured: 2 years

Secondary outcomes (3)

  1. Toxicity

    Measured: 2 years

  2. Pharmacodynamic response

    Measured: 2 years

  3. Activity of belinostat and bortezomib

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01075425
Sponsor's protocol ID
MCC-12517
Other IDs
NCI-2010-00127, RC2CA148431
Status last verified
Apr 2016
First submitted
15 Feb 2010
Last updated
15 Apr 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, belinostat and laboratory biomarker analysis in people with Acute Lymphocytic Leukemia and Acute Myeloid Leukemia, run by Virginia Commonwealth University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase II doses for the combination of bortezomib and belinostat (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01075425.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2016.

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