Enasidenib study

CC-90007-CP-004

A Study of Perpetrator Drug Interactions of Enasidenib in AML Patients

Disease:

Acute Myeloid Leukaemia (AML)

Summary:

The bone marrow is like a factory, producing all types of blood cells. This process begins with immature stem cells in the bone marrow, and results in production of mature red cells, platelets and different types of white cells.
Acute myeloid leukaemia (AML) is an aggressive cancer of the bone marrow. In AML, there is an overproduction of immature white cells, known as blasts. These immature cells do not function properly to prevent and fight infection, and can result in production of inadequate numbers of red cells and platelets, which in turn may lead to anaemia, bleeding and bruising.
There are a range of molecular markers that may be mutated in abnormal cells in AML and may affect prognosis. One such marker is IDH-2. This is mutated in around 2-4% of AML.
New drugs targeting molecular mutations are being developed for treatment of AML – including drugs that target mutated IDH-2 (IDH-2 inhibitors).
The aim of this study is to understand the safety and activity of CC-90007, or Enasidenib (an IDH-2 inhibitor) in patients who have AML and who have been shown to have the IDH-2 mutation. The study is also investigating the effect of Enasidenib on the metabolism of compounds and medications that are not part of leukaemia treatment, but may be commonly taken for other medical and non-medical reasons (eg. caffeine, omeprazole, rosuvastatin, midazolam). This is because there is a potential interaction between these compounds and Enasidenib when taken concurrently, and the effect of co-administration has not yet been explored.

Eligibility:

Include, but not limited to, the following:

Inclusion Criteria:
1. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
2. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
3. Subject is ≥ 18 years of age at the time of signing the ICF.
4. Subject has either primary or secondary (associated with MDS,[MPN, or prior therapy) AML as defined in protocol eligibility criteria.
5. Subject meets the PRIOR THERAPY criteria, as defined in protocol.
6. Subject meets the DISEASE STATUS criteria, as defined in protocol.
7. Subject has ECOG performance status of 0-2.
8. Subject has IDH2 gene mutations revealed by local testing (within window as per protocol) in samples of bone marrow aspirate and/or peripheral blood.
9. Subject has adequate ORGAN FUNCTION, as defined in protocol.
10. Females of childbearing potential (FCBP)2 may participate, providing they meet the conditions as defined in protocol
11. Male subjects must agree to practice true abstinence or to the use of highly effective contraceptive methods as defined in protocol

Exclusion Criteria:
1. Subject is suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype.
2. Subject has AML secondary to chronic myeloid leukemia (CML).
3. Subject has received a targeted agent against an IDH2 mutation *See protocol for more info
4. Subject has received systemic anticancer therapy or radiotherapy < 14 days prior to the start of study treatment. *See protocol for more info
5. Subject has received non-cytotoxic or investigational agents < 14 days or 5 half-lives, whichever is longer, prior to the start of study treatment.
6. Subject has undergone hematopoietic stem cell transplantation (HSCT) within 60 days prior to the start of study treatment, or on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). *The use of a stable dose of oral steroid post-HSCT and/or topical steroids for ongoing skin GVHD is permitted.
7. Subject has persistent, clinically significant non-hematologic toxicities from prior therapies.
8. Subject has or is suspected of having central nervous system (CNS) leukemia. *see protocol for more info
9. Subject has active uncontrolled systemic fungal, bacterial, or viral infection as defined in protcol
10. Subject has immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
11. Subject has cardiac issues, as defined in protocol
12. Subject is known seropositive or is infected with human immunodeficiency virus (HIV) or has active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
13. Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
14. Subject has uncontrolled hypertension, as defined in protocol
15. Subject is a pregnant or lactating female.
16. Subject is known or suspected to have hypersensitivity to any of the components of PK probe compounds or study treatment. *See protocol for more info
17. Subject has QTc interval ≥ 480ms or other factors that increase the risk of QT prolongation or arrhythmic events *see protocol for more info
18. In conjunction with the restrictions, subject is taking CYP-sensitive substrate medications, as defined in protocol
19. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk or would prevent the subject from participating in the study.
20. Subject has any condition that confounds the ability to interpret data from the study.

Contact person:

Lewis Edwards
Email ledwards@linear.org.au
Phone +61 477 660 142


Email
Phone

Principal Investigator:

Dr Carolyn Grove

Sponsor:

Celgene Corporation

Phase:

I

Protocol Number:

CC-90007-CP-004

Trial Registration Number:

NCT03720366

Clinical Trials.gov

ANZ Clinical Trial Registry