Myelodysplastic SyndromesPhase 2NCT03493646
Evaluating in Vivo AZA Incorporation in Mononuclear Cells Following Vidaza or CC486
A Phase 2 study testing Azacitidine and CC-486 in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Kirby Institute at 11 sites in Australia.
Trial summary
Myelodysplastic Syndrome (MDS) is a group of blood disorders where the bone marrow does not produce enough mature red blood cells, white blood cells and platelets. In a healthy person, the bone marrow makes blood stem cells (immature cells, also called 'blasts') that become mature blood cells over time. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia
- What is being tested?
- Azacitidine and CC-486
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 11 sitesAustralia
- Study dates
- 18 May 2018to 21 Sep 2021
- Phase
- Phase 2
- 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
- Male or female, ≥ 18 years of age.
- Documented diagnosis of
- Myelodysplastic syndrome classified as intermediate-2 or high risk according to the IPSS, or
- AML with 20-30% marrow blasts and multi-lineage dysplasia, according to WHO classification, or
- 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.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Show all 11Show fewer
- Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:
- 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
- Have a negative serum pregnancy test at screening
- 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.
- Understand and voluntarily sign an informed consent document prior to any study- related assessments or procedures conducted.
Who cannot join
- 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.
- Prior allogeneic or autologous stem cell transplant.
- Prior exposure to a hypomethylating agent.
- Use of any of the following within 28 days prior to cycle 1, day 1:
- thrombopoiesis-stimulating agents ([TSAs]; eg, Romiplostim, Eltrombopag, Interleukin-11)
- ESAs (Erythropoiesis stimulating agent) and other RBC hematopoietic growth factors (eg, interleukin-3)
Show all 34Show fewer
- Hydroxyurea
- Any other investigational product from another clinical trial
- 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.
- 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.
- 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:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
- Significant active cardiac disease within the previous 6 months, including:
- New York Heart Association (NYHA) class IV congestive heart failure
- Unstable angina or angina requiring surgical or medical intervention; and/or
- Myocardial infarction
- Active systemic infection including:
- Ongoing signs/symptoms related to the infection without improvement despite appropriate anti-infectives
- Active Hepatitis B infection
- Subjects with Human Immunodeficiency Virus (HIV) or Hepatitis C infection will be considered individually by the coordinating principal investigator:
- 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.
- Any of the following laboratory abnormalities:
- Serum AST/SGOT or ALT/SGPT > 2.5 x ULN
- 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).
- 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
- Serum creatinine > 2.5 x ULN
- Absolute white blood cell count ≥ 20 x 109/L
- Known or suspected hypersensitivity to azacitidine, mannitol, its constituents, or to any other humanized monoclonal antibody.
- Pregnant or breast-feeding females.
- Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Australia11 sites
Calvary Mater Newcastle
Newcastle, New South Wales, 2298
Nepean Hospital
Penrith, New South Wales, 2750
Prince of Wales Hospital
Sydney, New South Wales, 2031
Royal North Shore Hospital
Sydney, New South Wales, 2065
Blacktown Hospital
Sydney, New South Wales, 2148
Liverpool Hospital
Sydney, New South Wales, 2170
Gosford and Wyong Hospitals
Sydney, New South Wales, 219
St George Hospital
Sydney, New South Wales, 2217
Royal Prince Alfred Hospital
Sydney, New South Wales
St Vincent's hospital
Sydney, New South Wales
Wollongong Hospital
Wollongong, New South Wales, 2500
About this study
Myelodysplastic Syndrome (MDS) is a group of blood disorders where the bone marrow does not produce enough mature red blood cells, white blood cells and platelets. In a healthy person, the bone marrow makes blood stem cells (immature cells, also called 'blasts') that become mature blood cells over time. In people with MDS, this process is affected and immature blood cells in the bone marrow do not mature fully to become healthy blood cells. This causes a lack of healthy blood cells that can function properly. With fewer healthy blood cells, infection, anaemia, or easy bleeding may occur. MDS can progress to acute myeloid leukaemia in 25-30% of patients, and if untreated it can be rapidly fatal.
The purpose of this study is to evaluate the standard treatment, azacitidine (Vidaza) given as an injection under the skin compared to the same medication (called CC-486) taken as a tablet by mouth. Vidaza is approved by the Australian Therapeutics Goods Administration (TGA) as standard treatment for MDS. CC-486 is an experimental treatment. This means it is not an approved treatment for MDS in Australia. CC-486 is being developed to increase convenience and make it easier for patients to continue their treatment. So far it has been given to over 870 patients in studies across the world. The treatment in the injection and the tablet is the same. Studies like this one are being done to ensure the tablet works in the same way as the standard injected treatment.
Vidaza is given by subcutaneous injection (ie under the skin) over an hour for 7 days every 4 weeks for as long as it continues to work. All study participants will receive active treatment (there is no placebo), and all participants will receive the standard injection for six treatment cycles followed by the new tablet medication taken once daily for 21 days every 4 weeks. This allows the researchers to compare the two ways of giving the medicine.
Read the detailed description
MDS is an insidious and largely incurable haematological malignancy that increasingly impacts on the well-being of our ageing population, and one for which there has been no significant therapeutic advance since the introduction of injectable AZA (Vidaza®) over a decade ago.
Furthermore, the basis for the effectiveness of Vidaza® or lack thereof is not known and attempts at identifying genes that are reactivated and induce HSC differentiation have generally been unrewarding. It is also unclear whether these drugs work by inducing cellular differentiation or triggering apoptosis of the abnormal clone by activating permissive gene transcription. Recently developed assays permit genome-wide mutation analysis and assessment of gene expression and methylation at gene regulatory regions. Combined with functional studies, these assays are powerful tools that could help identify why some patients respond and others don't and why patients relapse after initial response. They can also help provide molecular insights into specific genes or pathways that could be manipulated to overcome primary or secondary drug resistance to AZA.
Following the evaluation CC-486 safety in Phase 1 studies, a Phase 2, international, multicentre, randomized, open-label, parallel group study was launched and is currently recruiting to evaluate the efficacy and safety of CC-486 alone and in combination with durvalumab in participants with MDS who fail to achieve objective response to treatment with Vidaza®. However, at present there is no objective method of correlating clinical or molecular response with actual drug incorporation due to the lack of a robust assay to measure AZA incorporation in vivo.
This gap has now been filled by the recent development of a liquid chromatography-mass spectrometry (LC-MS) based assay that is effective in measuring AZA pharmacokinetics in vivo; "AZA-MS: a novel mass spectrometry method to determine the intracellular pharmacokinetics of AZA therapy in vivo" (Unnikrishnan et al Leukemia 2017) and we will for the first time be able to directly compare Vidaza® incorporation with CC486 incorporation in the same patient and measuring clinical and molecular response after six cycles of the former followed by six cycles of the latter. The primary objective of the trial is to determine whether there is greater AZA incorporation in DNA in blood progenitors following 21 days of CC486 than there is with 7 days of Vidaza® in a 28- day treatment cycle and whether incorporation is associated with greater clinical and/or molecular response.
The secondary objectives of the trial are based on outcomes from a compassionate access program conducted in NSW, Australia from 2008-09. MDS, MDS/AML and CMML patients who respond to Vidaza® were found to have a greater fraction of hematopoietic progenitor cells (HPCs) progressing through the cell cycle than patients who fail to respond to AZA (Unnikrishnan et al 2017). What is not known is whether increased replication is associated with increased AZA incorporation. The availability of an assay (AZA-MS) to measure AZA incorporation, and the ability to measure the fraction of replicative HPCs, forms the basis of the secondary objectives of this study.
When applying the AZA-MS assay to samples collected from the compassionate access program, we also noted that AZA non-responders either do not incorporate AZA derivatives in DNA following Vidaza® or do incorporate AZA to levels comparable to that of responders yet still fail to respond (Unnikrishnan et al Leukemia 2017). Mechanisms of pharmacologically overcoming resistance would be quite different in the two instances. Longitudinal measurements of derivative AZA incorporation in DNA can now be combined with assays to evaluate whether patients who do not respond despite adequate drug uptake fail to activate downstream processes such as interferon/immune pathway activation or display check-point inhibition. This study will provide data to support individualised alternatives to optimise future AZA therapy.
- Being tested
- Azacitidine, CC-486
- Keywords
- Myelodysplastic Syndrome, MDS, Acute Myeloid Leukemia, AML, Chronic Myelomonocytic Leukemia, CMML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza
75mg/m2 per day for 7 days of each 28 day cycle. Cycles 1-6
CC-486Drug
Also called Oral azacitidine
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.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine | Active comparator | 6 cycles of azacitidine (28 day cycle) Receives: Drug: Azacitidine |
| CC 486 | Experimental | 6 cycles CC 486 (28 day cycle) Receives: Drug: CC-486 |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA incorporation of Vidaza® compared to CC-486
DNA incorporation of Vidaza® compared to CC-486 as measured by the area under the curve (AUC) during the first 6 cycles compared to the area under the curve from cycles 7 to 12.
Measured: 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 outcomes (4)
DNA incorporation in bone marrow mononuclear cells
DNA incorporation in bone marrow mononuclear cells following Vidaza® compared to CC-486 as measured by the area under the curve (AUC) in cycle 6 compared to the AUC in cycle 7
Measured: At the end of cycle 6 compared to cycle 7. Each cycle is 28 days
DNA AZA derivative uptake
DNA AZA derivative uptake (measured by AUC) between responders and non-responders who are classified as having AZA uptake
Measured: end of Cycle 6 and 12
Proportion of cells undergoing the cell cycle
Proportion of cells undergoing the cell cycle for non-responders with AZA uptake vs non-responders without AZA uptake
Measured: end of Cycle 6 and 12. Each cycle is 28 days
Inflammatory markers, as measured by AUC, between responders and non-
Inflammatory markers, as measured by AUC, between responders and non-responders who are classified as having AZA uptake
Measured: end of Cycle 6 and 12. Each cycle is 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2018
- Study start18 May 2018
- Primary completion15 Sep 2020
- Study completion21 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Phase II open label multicentre study. All participants will commence with Vidaza for 6 cycles, followed by 6 cycles of CC 486 regardless of response to Vidaza
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kirby Institute
- Sponsor type
- Other government
- Collaborators
- Celgene
- Responsible party
- Sponsor
- Investigators
- John Pimanda, MD, Principal investigator, University of New South Wales
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03493646
- Sponsor's protocol ID
- 2018-01-AZA
- Other IDs
- VZ-CL-MDSAML-PI-13085
- Status last verified
- May 2024
- First submitted
- 27 Mar 2018
- Last updated
- 28 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating in Vivo AZA Incorporation in Mononuclear Cells Following Vidaza or CC486
- ClinicalTrials.gov ID
- NCT03493646
- Acronym / sponsor ID
- 2018-01-AZA
- Keywords
- Myelodysplastic Syndrome, MDS, Acute Myeloid Leukemia, AML, Chronic Myelomonocytic Leukemia, CMML
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Kirby InstituteOther government
- Collaborators
- Celgene
- Study start
- 18 May 2018 (actual)
- Primary completion
- 15 Sep 2020 (actual)
- Study completion
- 21 Sep 2021 (actual)
- First posted
- 10 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Myelodysplastic Syndrome (MDS) is a group of blood disorders where the bone marrow does not produce enough mature red blood cells, white blood cells and platelets. In a healthy person, the bone marrow makes blood stem cells (immature cells, also called 'blasts') that become mature blood cells over time. In people with MDS, this process is affected and immature blood cells in the bone marrow do not mature fully to become healthy blood cells. This causes a lack of healthy blood cells that can function properly. With fewer healthy blood cells, infection, anaemia, or easy bleeding may occur. MDS can progress to acute myeloid leukaemia in 25-30% of patients, and if untreated it can be rapidly fatal.
The purpose of this study is to evaluate the standard treatment, azacitidine (Vidaza) given as an injection under the skin compared to the same medication (called CC-486) taken as a tablet by mouth. Vidaza is approved by the Australian Therapeutics Goods Administration (TGA) as standard treatment for MDS. CC-486 is an experimental treatment. This means it is not an approved treatment for MDS in Australia. CC-486 is being developed to increase convenience and make it easier for patients to continue their treatment. So far it has been given to over 870 patients in studies across the world. The treatment in the injection and the tablet is the same. Studies like this one are being done to ensure the tablet works in the same way as the standard injected treatment.
Vidaza is given by subcutaneous injection (ie under the skin) over an hour for 7 days every 4 weeks for as long as it continues to work. All study participants will receive active treatment (there is no placebo), and all participants will receive the standard injection for six treatment cycles followed by the new tablet medication taken once daily for 21 days every 4 weeks. This allows the researchers to compare the two ways of giving the medicine.
Detailed description
MDS is an insidious and largely incurable haematological malignancy that increasingly impacts on the well-being of our ageing population, and one for which there has been no significant therapeutic advance since the introduction of injectable AZA (Vidaza®) over a decade ago.
Furthermore, the basis for the effectiveness of Vidaza® or lack thereof is not known and attempts at identifying genes that are reactivated and induce HSC differentiation have generally been unrewarding. It is also unclear whether these drugs work by inducing cellular differentiation or triggering apoptosis of the abnormal clone by activating permissive gene transcription. Recently developed assays permit genome-wide mutation analysis and assessment of gene expression and methylation at gene regulatory regions. Combined with functional studies, these assays are powerful tools that could help identify why some patients respond and others don't and why patients relapse after initial response. They can also help provide molecular insights into specific genes or pathways that could be manipulated to overcome primary or secondary drug resistance to AZA.
Following the evaluation CC-486 safety in Phase 1 studies, a Phase 2, international, multicentre, randomized, open-label, parallel group study was launched and is currently recruiting to evaluate the efficacy and safety of CC-486 alone and in combination with durvalumab in participants with MDS who fail to achieve objective response to treatment with Vidaza®. However, at present there is no objective method of correlating clinical or molecular response with actual drug incorporation due to the lack of a robust assay to measure AZA incorporation in vivo.
This gap has now been filled by the recent development of a liquid chromatography-mass spectrometry (LC-MS) based assay that is effective in measuring AZA pharmacokinetics in vivo; "AZA-MS: a novel mass spectrometry method to determine the intracellular pharmacokinetics of AZA therapy in vivo" (Unnikrishnan et al Leukemia 2017) and we will for the first time be able to directly compare Vidaza® incorporation with CC486 incorporation in the same patient and measuring clinical and molecular response after six cycles of the former followed by six cycles of the latter. The primary objective of the trial is to determine whether there is greater AZA incorporation in DNA in blood progenitors following 21 days of CC486 than there is with 7 days of Vidaza® in a 28- day treatment cycle and whether incorporation is associated with greater clinical and/or molecular response.
The secondary objectives of the trial are based on outcomes from a compassionate access program conducted in NSW, Australia from 2008-09. MDS, MDS/AML and CMML patients who respond to Vidaza® were found to have a greater fraction of hematopoietic progenitor cells (HPCs) progressing through the cell cycle than patients who fail to respond to AZA (Unnikrishnan et al 2017). What is not known is whether increased replication is associated with increased AZA incorporation. The availability of an assay (AZA-MS) to measure AZA incorporation, and the ability to measure the fraction of replicative HPCs, forms the basis of the secondary objectives of this study.
When applying the AZA-MS assay to samples collected from the compassionate access program, we also noted that AZA non-responders either do not incorporate AZA derivatives in DNA following Vidaza® or do incorporate AZA to levels comparable to that of responders yet still fail to respond (Unnikrishnan et al Leukemia 2017). Mechanisms of pharmacologically overcoming resistance would be quite different in the two instances. Longitudinal measurements of derivative AZA incorporation in DNA can now be combined with assays to evaluate whether patients who do not respond despite adequate drug uptake fail to activate downstream processes such as interferon/immune pathway activation or display check-point inhibition. This study will provide data to support individualised alternatives to optimise future AZA therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase II open label multicentre study. All participants will commence with Vidaza for 6 cycles, followed by 6 cycles of CC 486 regardless of response to Vidaza
| Arm | Type | Receives |
|---|---|---|
| Azacitidine | Active comparator | Drug: Azacitidine6 cycles of azacitidine (28 day cycle) |
| CC 486 | Experimental | Drug: CC-4866 cycles CC 486 (28 day cycle) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female, ≥ 18 years of age.
- Documented diagnosis of
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:
- 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.
Key exclusion criteria (34 listed)
- 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.
- Prior allogeneic or autologous stem cell transplant.
- Prior exposure to a hypomethylating agent.
- Use of any of the following within 28 days prior to cycle 1, day 1:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: Vidaza75mg/m2 per day for 7 days of each 28 day cycle. Cycles 1-6 | Drug | Azacitidine |
| CC-486Also: Oral azacitidine100 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. | Drug | CC 486 |
Primary outcome
DNA incorporation of Vidaza® compared to CC-486
Time frame: At the end of cycle 6 (cycles 1-6 inclusive) compared with cycles 7-12 (cycles 7-12 inclusive). Each cycle is 28 days
DNA incorporation of Vidaza® compared to CC-486 as measured by the area under the curve (AUC) during the first 6 cycles compared to the area under the curve from cycles 7 to 12.
4 secondary outcomes
DNA incorporation in bone marrow mononuclear cells
Time frame: At the end of cycle 6 compared to cycle 7. Each cycle is 28 days
DNA AZA derivative uptake
Time frame: end of Cycle 6 and 12
Proportion of cells undergoing the cell cycle
Time frame: end of Cycle 6 and 12. Each cycle is 28 days
Inflammatory markers, as measured by AUC, between responders and non-
Time frame: end of Cycle 6 and 12. Each cycle is 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Pimanda, MD principal investigator
University of New South Wales
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine and CC-486 in people with Myelodysplastic Syndromes and Acute Myeloid Leukemia, run by Kirby Institute at 11 sites in Australia.
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 11 inclusion and 34 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 28 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Australia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
DNA incorporation of Vidaza® compared to CC-486 (time frame: At the end of cycle 6 (cycles 1-6 inclusive) compared with cycles 7-12 (cycles 7-12 inclusive). Each cycle is 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 May 2024.