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

NCT03493646 | Completed Phase 2

• 2 other identifiers: 2018-01-AZAVZ-CL-MDSAML-PI-13085
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Myelodysplastic Syndromes; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Keywords

Myelodysplastic Syndrome; MDS; Acute Myeloid Leukemia; AML; Chronic Myelomonocytic Leukemia; CMML

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  At the end of cycle 6 compared to cycle 7. Each cycle is 28 days

• DNA AZA derivative uptake

  end of Cycle 6 and 12

• Proportion of cells undergoing the cell cycle

  end of Cycle 6 and 12. Each cycle is 28 days

• Inflammatory markers, as measured by AUC, between responders and non-

  end of Cycle 6 and 12. Each cycle is 28 days

Study Arms (2)

Azacitidine

ACTIVE COMPARATOR

6 cycles of azacitidine (28 day cycle)

Drug: Azacitidine

CC 486

EXPERIMENTAL

6 cycles CC 486 (28 day cycle)

Drug: CC-486

Interventions

Azacitidine DRUG

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

Also known as: Vidaza

Azacitidine

CC-486 DRUG

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.

Also known as: Oral azacitidine

CC 486

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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)
• 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:

Sponsors & Collaborators

• Kirby Institute: lead
• Celgene: collaborator

Study Sites (11)

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Nepean Hospital

Penrith, New South Wales, 2750, Australia

Location

Prince of Wales Hospital

Sydney, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, 2065, Australia

Location

Blacktown Hospital

Sydney, New South Wales, 2148, Australia

Location

Liverpool Hospital

Sydney, New South Wales, 2170, Australia

Location

Gosford and Wyong Hospitals

Sydney, New South Wales, 219, Australia

Location

St George Hospital

Sydney, New South Wales, 2217, Australia

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia

Location

St Vincent's hospital

Sydney, New South Wales, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Interventions

Azacitidine; cc-486

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• John Pimanda, MD

  University of New South Wales

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 10, 2018
• Study Start: May 18, 2018
• Primary Completion: September 15, 2020
• Study Completion: September 21, 2021
• Last Updated: May 28, 2024

Record last verified: 2024-05

Locations

AU (11)