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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03493646




Registration number
NCT03493646
Ethics application status
Date submitted
27/03/2018
Date registered
10/04/2018

Titles & IDs
Public title
Evaluating in Vivo AZA Incorporation in Mononuclear Cells Following Vidaza or CC486
Scientific title
Evaluating in Vivo AZA Incorporation in Mononuclear Cells Following Vidaza or CC486
Secondary ID [1] 0 0
VZ-CL-MDSAML-PI-13085
Secondary ID [2] 0 0
2018-01-AZA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Acute Myeloid Leukemia 0 0
Chronic Myelomonocytic Leukemia 0 0
Condition category
Condition code
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Treatment: Drugs - CC-486

Active comparator: Azacitidine - 6 cycles of azacitidine (28 day cycle)

Experimental: CC 486 - 6 cycles CC 486 (28 day cycle)


Treatment: Drugs: Azacitidine
75mg/m2 per day for 7 days of each 28 day cycle. Cycles 1-6

Treatment: Drugs: CC-486
100 mg BID for the first 21 days of each 28-day treatment cycle (cycles 7-8). The dose should be increased from cycle 9 onwards to 150mg BID for the first 21 days of each 28-day treatment cycle (cycles 9-12) in the absence of Grade 3 or 4 AE. If 2 or more cycles are tolerated at this dose, further increments are permitted for patients with Stable Disease or if clinically indicated in consultation with the coordinating investigator as per the study dose modification schedule.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DNA incorporation of Vidaza® compared to CC-486
Timepoint [1] 0 0
At the end of cycle 6 (cycles 1-6 inclusive) compared with cycles 7-12 (cycles 7-12 inclusive). Each cycle is 28 days
Secondary outcome [1] 0 0
DNA incorporation in bone marrow mononuclear cells
Timepoint [1] 0 0
At the end of cycle 6 compared to cycle 7. Each cycle is 28 days
Secondary outcome [2] 0 0
DNA AZA derivative uptake
Timepoint [2] 0 0
end of Cycle 6 and 12
Secondary outcome [3] 0 0
Proportion of cells undergoing the cell cycle
Timepoint [3] 0 0
end of Cycle 6 and 12. Each cycle is 28 days
Secondary outcome [4] 0 0
Inflammatory markers, as measured by AUC, between responders and non-
Timepoint [4] 0 0
end of Cycle 6 and 12. Each cycle is 28 days

Eligibility
Key inclusion criteria
1. Male or female, = 18 years of age.
2. Documented diagnosis of

1. Myelodysplastic syndrome classified as intermediate-2 or high risk according to the IPSS, or
2. AML with 20-30% marrow blasts and multi-lineage dysplasia, according to WHO classification, or
3. CMML with 10-29% marrow blasts without myeloproliferative disorder according to WHO classification, or Confirmation will be from either the BMA performed at screening or a standard of care BMA if performed up to 6 weeks before cycle 1 day 1.
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
4. Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:

1. Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; true abstinence; or vasectomized partner) throughout the study, and for 90 days following the last dose of investigational product (IP); and
2. Have a negative serum pregnancy test at screening
5. Male participants with a female partner of childbearing potential must agree to use at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 90 days following the last dose of Investigational Product.
6. Understand and voluntarily sign an informed consent document prior to any study- related assessments or procedures conducted.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Acute myeloid leukemia (AML) - = 30% blasts in bone marrow according to WHO classification. Participants known to have = 30% blasts are not eligible for inclusion in this study. Recognizing limitations of blast cell quantitation, this protocol will allow participants with pre-enrollment (screening/baseline) bone marrow blast counts up to 33% to be considered for inclusion subject to discussion with the Coordinating PI prior to enrollment.
2. Prior allogeneic or autologous stem cell transplant.
3. Prior exposure to a hypomethylating agent.
4. Use of any of the following within 28 days prior to cycle 1, day 1:

1. thrombopoiesis-stimulating agents ([TSAs]; eg, Romiplostim, Eltrombopag, Interleukin-11)
2. ESAs (Erythropoiesis stimulating agent) and other RBC hematopoietic growth factors (eg, interleukin-3)
3. Hydroxyurea
4. Any other investigational product from another clinical trial
5. Concurrent use of corticosteroids unless the participant is on a stable or decreasing dose for = 1 week prior to enrollment for medical conditions other than MDS.
6. History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the IP and/or predispose the participant to an increased risk of gastrointestinal toxicity.
7. Prior history of malignancies, other than MDS, unless the participant has been free of the disease for = 3 years. However, participants with the following history/concurrent conditions are allowed:

1. Basal or squamous cell carcinoma of the skin
2. Carcinoma in situ of the cervix
3. Carcinoma in situ of the breast
4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
8. Significant active cardiac disease within the previous 6 months, including:

1. New York Heart Association (NYHA) class IV congestive heart failure
2. Unstable angina or angina requiring surgical or medical intervention; and/or
3. Myocardial infarction
9. Active systemic infection including:

1. Ongoing signs/symptoms related to the infection without improvement despite appropriate anti-infectives
2. Active Hepatitis B infection
3. Subjects with Human Immunodeficiency Virus (HIV) or Hepatitis C infection will be considered individually by the coordinating principal investigator:

i) Those with HIV will generally be eligible if receiving antiretroviral therapy, HIV VL is suppressed <50 copies/mL and CD4=350 cells/mm3. ii) Those with HCV will generally be eligible if there is no evidence of clinical hepatic dysfunction or other systemic manifestations of HCV disease and the hepatic parameters below are met. Consideration should be given to curative HCV therapy prior to enrollment in consultation with HCV clinician, if possible.
10. Any of the following laboratory abnormalities:

1. Serum AST/SGOT or ALT/SGPT > 2.5 x ULN
2. Serum total bilirubin > 1.5 x ULN. Higher levels are acceptable if these can be attributed to active RBC precursor destruction within the bone marrow (ie, ineffective erythropoiesis).
3. Evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Direct Antiglobulin Test or over 50% of indirect bilirubin
4. Serum creatinine > 2.5 x ULN
5. Absolute white blood cell count = 20 x 109/L
11. Known or suspected hypersensitivity to azacitidine, mannitol, its constituents, or to any other humanized monoclonal antibody.
12. Pregnant or breast-feeding females.
13. Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
14. Any condition not already outlined above which, in the opinion of the clinical investigator, would place the subject at risk if they participated or would jeopardise adherence or follow up or confound the ability to interpret study data.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Other
Other design features
Phase
Phase 2
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
18/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/09/2021
Sample size
Target
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [2] 0 0
Nepean Hospital - Penrith
Recruitment hospital [3] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [4] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [5] 0 0
Blacktown Hospital - Sydney
Recruitment hospital [6] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [7] 0 0
Gosford and Wyong Hospitals - Sydney
Recruitment hospital [8] 0 0
St George Hospital - Sydney
Recruitment hospital [9] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment hospital [10] 0 0
St Vincent's hospital - Sydney
Recruitment hospital [11] 0 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 0 0
2298 - Newcastle
Recruitment postcode(s) [2] 0 0
2750 - Penrith
Recruitment postcode(s) [3] 0 0
2031 - Sydney
Recruitment postcode(s) [4] 0 0
2065 - Sydney
Recruitment postcode(s) [5] 0 0
2148 - Sydney
Recruitment postcode(s) [6] 0 0
2170 - Sydney
Recruitment postcode(s) [7] 0 0
219 - Sydney
Recruitment postcode(s) [8] 0 0
2217 - Sydney
Recruitment postcode(s) [9] 0 0
- Sydney
Recruitment postcode(s) [10] 0 0
2500 - Wollongong

Funding & Sponsors
Primary sponsor type
Government body
Name
Kirby Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Celgene
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Pimanda, MD
Address 0 0
University of New South Wales
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03493646