Clinical Trials /

A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia

NCT03451084

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
  • Official Title: A Phase IIA Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: ASLAN003-003
  • NCT ID: NCT03451084

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
ASLAN003Part 1: Dose Level 1

Purpose

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.

Detailed Description

      ASLAN003-003 is a multi-center, Phase IIA study to determine the optimum dose of ASLAN003
      based on the safety, efficacy, and tolerability of varying doses of ASLAN003 (100 mg QD, 200
      mg QD, 100 mg BID, and possibly 200 mg BID) administered to AML subjects daily for a
      continuous 28-day treatment cycle until disease relapse, disease progression, unacceptable
      toxicity, or withdrawal of consent.

      The study has 2 parts and plans to enroll a total of 44 to 56 patients with 18 to 24 patients
      in Part 1 and 26 to 32 patients in Part 2 (comprising Parts 2A and 2B). The Overall Complete
      Remission Rate will be evaluated in AML patients not eligible for standard treatment (Part 1)
      and in relapsed and refractory AML patients (Part 2A) using the optimum dose of ASLAN003
      established in Part 1 of the study. In Part 2B of the study, 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 will be determined.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose Level 1Experimental
  • ASLAN003
Part 1: Dose Level 2Experimental
  • ASLAN003
Part 1: Dose Level 3Experimental
  • ASLAN003
Part 1: Dose Level 4Experimental
  • ASLAN003
Part 2:ASLAN003 at Optinum Dose Level -1 & AzacitidineExperimental
  • ASLAN003
Part 2:ASLAN003 at Optinum Dose Level & AzacitidineExperimental
  • ASLAN003

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall complete remission rate
Time Frame:4 months after LPI
Safety Issue:
Description:Defined as the proportion of patients with a best response of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), defined in accordance with the IWG Response Criteria in AML from day 29. Treatment failure is defined as not achieving any response 4 months after study treatment.

Secondary Outcome Measures

Measure:Incidence of Adverse Events (AEs)
Time Frame:Through 28 days post last study medication administration
Safety Issue:
Description:Incidence of AEs, categorized in accordance to CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests)
Measure:Relapse Free Survival
Time Frame:Through study completion, an average of 6 months.
Safety Issue:
Description:Defined as the time the criteria for remission (CR or CRi) are first met until there is evidence of patient relapse, regardless of whether the patient is still taking study drug.
Measure:Clinical Benefit Rate
Time Frame:4 months after LPI
Safety Issue:
Description:Defined as the proportion of patients with an AML IWG best response of CR, CRi or PR.
Measure:Tumor % change
Time Frame:29 days after LPI
Safety Issue:
Description:Tumor % change from baseline in BM blasts at Day 29.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aslan Pharmaceuticals

Trial Keywords

  • AML, ASLAN, DHODH

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