A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: ASLAN003
Intervention description: Patients will be administered with the study drug, ASLAN003. The study drug is to be administered orally, QD or BID. It is recommended to administer the study drug with food or within 30 minutes after food intake.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: AML, ASLAN, DHODH

Summary:

      ASLAN003-003 is a multi-center, Phase IIA study to evalute the efficacy of ASLAN003 in AML
      patients who are ineligible for standard treatment with an expansion cohort in
      relapsed/refractory patients, and to determine the appropriate dose of ASLAN003 in
      combination with azacitidine in older (more than or equal to 60 years) AML patients who have
      exhausted any approved and available treatment options.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients who are of or older than 18 years old in the United States or are of or older
             than the legal age in the respective countries at the time when written informed
             consent is obtained

          2. Patients who are able to understand and willing to sign the informed consent form
             (ICF)

          3. Patients who are diagnosed with AML according to the 2016 revision to the World Health
             Organization classification of myeloid neoplasms and acute leukemia (refer to Appendix
             1: WHO Classification of Acute Myeloid Leukemia)

          4. Patients who have a sufficient archival or fresh BM aspiration sample for the
             evaluation of relevant exploratory endpoint.

        Note: Patients who do not have sufficient archival BM aspiration sample and refuse to
        repeat the procedure may be enrolled in the trial only after written confirmation by ASLAN
        5. Part 1: Patients who are ineligible for standard treatment of AML including to the
        following conditions:

          -  Patients who are ineligible for chemotherapy, and have exhausted any approved and
             available treatment options. More details on patients who are considered as ineligible
             or unfit for chemotherapy as per Ferrara et al, Leukemia, 2013 can be found in
             Appendix 4.

          -  Patients who have relapsed from prior remission;

          -  Patients who have failed to respond to prior therapy including chemotherapy,
             hypomethylating agents, and bone marrow transplantation.

             5. Part 2A: Patients who have relapsed or refractory AML to treatments including
             chemotherapy, hypomethylating agents, bone marrow transplantation, and other
             anti-leukemic agents

               -  Relapsed patients who have bone marrow blasts ≥5%; or reappearance of blasts in
                  the blood; or development of extramedullary disease after prior CR or CRi

               -  Refractory patients who have no CR or CRi after 2 courses of intensive induction
                  treatment 5. Part 2B: Older patients (more than or equal to 60 years) AML
                  patients who have exhausted any approved and available treatment options.

                  6. Patients who have an ECOG performance status of ≤ 2 7. Patients with adequate
                  renal and hepatic function, as defined below:

          -  Estimated Glomerular Filtration Rate (eGFR) or creatinine clearance (CrCl) (CrCl
             calculated by the Cockroft and Gault method) ≥ 40 ml/min/1.73 m2

          -  Total bilirubin, AST, and ALT ≤ 1.5 × ULN

        Exclusion Criteria:

          1. Patients who are diagnosed with de novo myeloid sarcoma without BM involvement

          2. Patients who are diagnosed with acute promyelocytic leukemia/retinoic acid receptor
             alpha (PML-RARA)

          3. Patients who received any other standard or investigational treatment for their
             leukemia within the last 7 days before starting the first dose of study drug, with the
             exception of leukapheresis and hydroxyurea

          4. Patients with unresolved serious toxicity (≥ CTCAE 4.03 Grade 2) from prior
             administration of standard or investigational treatment for their leukemia

          5. Patients who have a positive test for human immunodeficiency virus (HIV), viral
             hepatitis C infection (patients with sustained viral response are not excluded),
             active viral hepatitis B infection (positive hepatitis B surface antigen [HBsAg]) with
             hepatitis B virus deoxyribonucleic acid (DNA) exceeding 2000 IU/ml

          6. Patients who have a known history of liver cirrhosis Child-Pugh score B or C

          7. Patients who have any history of other malignancy unless in remission for more than 1
             year (skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative
             intent is not exclusionary)

          8. Female patients who are pregnant or breast-feeding

          9. Patients with a known history of alcohol or drug addiction on the basis that there
             could be a higher risk of non-compliance to study treatment

         10. Patients with a history or presence of a clinically significant condition which in the
             opinion of the Investigator could jeopardize the safety of the patient or the validity
             of the study results

         11. Patients who have been previously treated with ASLAN003