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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00351975




Registration number
NCT00351975
Ethics application status
Date submitted
13/07/2006
Date registered
13/07/2006
Date last updated
22/12/2014

Titles & IDs
Public title
Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases
Scientific title
A Phase I Study of PXD101 in Combination With Azacitidine (5-Aza) for Advanced Hematologic Malignancies
Secondary ID [1] 0 0
NCI-2009-00146
Secondary ID [2] 0 0
NCI-2009-00146
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Accelerated Phase of Disease 0 0
Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11 0 0
Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11 0 0
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1 0 0
Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL 0 0
Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA 0 0
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative 0 0
Blastic Phase 0 0
Chronic Myelogenous Leukemia, BCR-ABL1 Positive 0 0
Chronic Myelomonocytic Leukemia 0 0
de Novo Myelodysplastic Syndrome 0 0
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable 0 0
Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia 0 0
Previously Treated Myelodysplastic Syndrome 0 0
Primary Myelofibrosis 0 0
Recurrent Adult Acute Lymphoblastic Leukemia 0 0
Recurrent Adult Acute Myeloid Leukemia 0 0
Recurrent Disease 0 0
Secondary Acute Myeloid Leukemia 0 0
Secondary Myelodysplastic Syndrome 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Belinostat
Treatment: Drugs - Azacitidine
Other interventions - Laboratory Biomarker Analysis

Experimental: Arm I (chemotherapy) - Patients receive azacitidine SC on days 1-5.

Experimental: Arm II (chemotherapy, enzyme inhibitor therapy) - Patients receive azacitidine as in arm I and belinostat at the MTD IV over 30 minutes on days 1-5.


Treatment: Drugs: Belinostat
Given IV

Treatment: Drugs: Azacitidine
Given SC

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Course 1 (28 days)
Secondary outcome [1] 0 0
Changes in pharmacodynamic variables (target gene expression, apoptosis) - Compared between the two groups using two-sample t tests.
Timepoint [1] 0 0
Course 1 (baseline to day 5)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, days 4 or 5, and days 25-28
Secondary outcome [3] 0 0
Clinical activity (complete remission, partial remission, stable disease, hematologic improvement) - Recorded and tabulated for both the MTD and randomized cohorts.
Timepoint [3] 0 0
After 4, 8, and 16 weeks

Eligibility
Key inclusion criteria
- 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

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Wisconsin
Country [3] 0 0
Canada
State/province [3] 0 0
Ontario
Country [4] 0 0
New Zealand
State/province [4] 0 0
Canterbury

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/show/NCT00351975
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Olatoyosi Odenike
Address 0 0
University of Chicago Comprehensive Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications