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Accelerated Phase of DiseasePhase 1NCT00351975

Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

A Phase 1 study testing Belinostat, Azacitidine and Laboratory Biomarker Analysis in people with Accelerated Phase of Disease and Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11, run by National Cancer Institute (NCI) at 4 sites in 3 countries.

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

This phase I trial is studying the side effects and best dose of belinostat when given together with azacitidine in treating patients with advanced hematologic cancers or other diseases. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Belinostat, Azacitidine and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
4 sitesin 3 countries
Study dates
Jun 2006to Mar 2013
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

  • Histologically confirmed diagnosis of 1 of the following:
  • Relapsed or refractory acute myeloid leukemia (AML)
  • Relapsed or refractory acute promyelocytic leukemia (must have failed both tretinoin and arsenic trioxide)
  • Relapsed or refractory acute lymphoblastic leukemia
  • Secondary AML, including AML arising from antecedent hematologic diseases, such as myelodysplastic syndromes (MDS) or myeloproliferative disorders, OR therapy-related AML
  • Chronic myelogenous leukemia in accelerated or blast phase
Show all 53Show fewer
  • Advanced phases of Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders, as defined by ≥ 1 of the following:
  • Presence of anemia (hemoglobin < 10 g/dL and/or red blood cell transfusion dependent)
  • Presence of palpable splenomegaly
  • MDS, including chronic myelomonocytic leukemia
  • Must have intermediate or high-risk International Prognostic Scoring System (IPSS) scores (≥ 0.5)
  • Low-risk IPSS scores allowed provided ≥ 1 of the following criteria are met:
  • Hemoglobin < 10 g/dL and/or red blood cell transfusion dependent
  • Platelet count < 50,000/mm³
  • Absolute neutrophil count < 1,000/mm³
  • Refractory disease OR no standard therapy exists
  • Evidence of AML associated with dysplasia on bone marrow histology for elderly patients (i.e., > 60 years old) who are previously untreated and not candidates for or unwilling to undergoing induction therapy
  • No known active CNS involvement with disease
  • CALGB performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
  • ALT ≤ 3 times upper limit of normal (unless due to disease)
  • Creatinine ≤ 2 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101 or Azacitidine
  • No history of allergic reactions to mannitol
  • No history of dose-limiting toxicity during prior treatment with Azacitidine
  • No concurrent uncontrolled illness including, but not limited to, the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude compliance with study requirements
  • No marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 500 msec)
  • No long QT syndrome
  • No uncontrolled cardiovascular disease, including the following:
  • Severe uncontrolled hypertension
  • Uncontrolled congestive heart failure related to primary cardiac disease
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled ischemic or severe valvular heart disease
  • Myocardial infarction within the past 6 months
  • See Disease Characteristics
  • Recovered from prior therapy
  • At least 2 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
  • At least 2 weeks since prior radiotherapy
  • At least 4 weeks since prior investigational agents
  • At least 24 hours since prior hydroxyurea
  • At least 2 weeks since prior valproic acid
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No concurrent medication that may cause torsade de pointes
  • No other concurrent anticancer therapy, including chemotherapy, radiotherapy, or biological agents

Who cannot join

None listed.

Trial locations and contacts

4 sites in 3 countries.

4 sites in 3 countries

United States2 sites

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

New Zealand1 site

  • Princess Margaret Hospital

    Cashmere, Canterbury, 8022

Other trials in New Zealand

About this study

Official title: A Phase I Study of PXD101 in Combination With Azacitidine (5-Aza) for Advanced Hematologic Malignancies

This phase I trial is studying the side effects and best dose of belinostat when given together with azacitidine in treating patients with advanced hematologic cancers or other diseases. Belinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving belinostat together with azacitidine may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of PXD101 (belinostat) when given in combination with azacitidine (when azacitidine is utilized at a dose range where its effects on cellular differentiation are known to be predominant) in patients with advanced hematologic cancers or other diseases.

SECONDARY OBJECTIVES:

  1. Identify any additive or synergistic effects of this regimen on pharmacodynamic parameters, including apoptosis and re-expression of specific target genes.

II. Assess any evidence of clinical activity (complete remission, partial remission, hematologic improvement, stable disease) of this regimen in these patients.

OUTLINE: This is a dose-escalation study of belinostat followed by a randomized study.

Patients receive azacitidine subcutaneously (SC) and belinostat intravenously (IV) over 30 minutes on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of belinostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, additional patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (with trilineage dysplasia or arising from MDS) are randomized to 1 of 2 treatment arms.

Arm I: Patients receive azacitidine SC on days 1-5.

Arm II: Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After receiving one course, patients randomized to arm I may crossover to receive treatment on arm II.

For patients enrolled in the randomized portion of the study, bone marrow aspirates are obtained at baseline, and after course 1 for correlative studies. Samples are examined by gene expression analysis of p15 and p21, DNA methylation of p15INK4B, and apoptosis by RT-PCR and flow cytometry. Pharmacodynamic assays are also performed.

After completion of study treatment, patients are followed periodically for up to 2 years.

Being tested
Belinostat, Azacitidine, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Myelomonocytic, Acute, Leukemia, Promyelocytic, Acute, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Chronic, Myeloproliferative Disorders, Primary Myelofibrosis

What participants receive

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

  • BelinostatDrug

    Also called Beleodaq, PXD 101, PXD101

    Given IV

  • AzacitidineDrug

    Also called 5-AC, 5-AZC, U-18496

    Given SC

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00351975
Study groupRoleWhat they receive
Arm I (chemotherapy)ExperimentalPatients receive azacitidine SC on days 1-5.
Receives: Drug: Azacitidine; Other: Laboratory Biomarker Analysis
Arm II (chemotherapy, enzyme inhibitor therapy)ExperimentalPatients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.
Receives: Drug: Belinostat; Drug: Azacitidine; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Maximum tolerated dose of belinostat in combination with azacitidine

    Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 or 4.0.

    Measured: Course 1 (28 days)

Secondary outcomes (3)

  1. Changes in pharmacodynamic variables (target gene expression, apoptosis)

    Compared between the two groups using two-sample t tests.

    Measured: Course 1 (baseline to day 5)

  2. Association of methylation status, categorized as positive or negative, with changes in target gene expression

    Distinguished by sequence-specific polymerase chain reaction (PCR) primers. Compared using a two-sample t or Wilcoxon nonparametric test.

    Measured: Baseline, days 4 or 5, and days 25-28

  3. Clinical activity (complete remission, partial remission, stable disease, hematologic improvement)

    Recorded and tabulated for both the MTD and randomized cohorts.

    Measured: After 4, 8, and 16 weeks

Timeline

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

  1. First posted14 Jul 2006 (estimated)
  2. Study startJun 2006
  3. Primary completionMar 2013
  4. Study completionMar 2013

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00351975
Sponsor's protocol ID
NCI-2009-00146
Other IDs
NCI-2009-00146, UCCRC-14510A, NCI-7285, CDR0000486418, 14510A, 7285, U01CA069852, U01CA132123
Status last verified
Oct 2013
First submitted
13 Jul 2006
Last updated
23 Dec 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Belinostat, Azacitidine and Laboratory Biomarker Analysis in people with Accelerated Phase of Disease and Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11, run by National Cancer Institute (NCI) at 4 sites in 3 countries.

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 53 inclusion and 0 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 23 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada, New Zealand. 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?

Maximum tolerated dose of belinostat in combination with azacitidine (time frame: Course 1 (28 days)). 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 NCT00351975.

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 23 Dec 2014.

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