Evaluating in Vivo AZA Incorporation in Mononuclear Cells Following Vidaza or CC486

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kirby Institute
• Collaborator: Celgene
• Treatments: Azacitidine; Cc-486

Criteria

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.

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.