A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia

NCT03451084 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ASLAN003-003
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 8

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

AML, ASLAN, DHODH

Outcome Measures

Primary Outcomes (3)

• Overall Complete Remission Rate

  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. IWG Response Criteria in AML defines CR or CRi as: 1. Complete remission (CR): Bone marrow blasts \<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0 x 109/L (1000/µL); platelet count \>100 x 109/L (100,000/µL); independence of red cell transfusions 2. CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia (\<1.0 x 109/L (1000/µL)) or thrombocytopenia (\<100 x 109/L (100,000/µL))

  4 months after study treatment

• Number of Participants With Adverse Events

  Number of Participants with Adverse Events reported through 28 days post last study medication administration

  Through 28 days post last study medication administration

• Safety Assessments

  Safety Assessments - Clinical laboratory test: Hematology and Chemistry

  Through 28 days post last study medication administration

Secondary Outcomes (3)

• Relapse Free Survival

  From 12 weeks post end of treatment (EOT) until the date of first documented relapse or date of death from any cause, whichever came first, assessed up to 24 months

• Clinical Benefit Rate

  4 months after study treatment

• % Change From Baseline in BM Blasts at Day 29

  Baseline and day 29

Study Arms (6)

Part 1: Dose Level 1

EXPERIMENTAL

Drug: ASLAN003

Part 1: Dose Level 2

EXPERIMENTAL

Drug: ASLAN003

Part 1: Dose Level 3

EXPERIMENTAL

Drug: ASLAN003

Part 1: Dose Level 4

EXPERIMENTAL

Drug: ASLAN003

Part 2:ASLAN003 at Optinum Dose Level -1 & Azacitidine

EXPERIMENTAL

Drug: ASLAN003

Part 2:ASLAN003 at Optinum Dose Level & Azacitidine

EXPERIMENTAL

Drug: ASLAN003

Interventions

ASLAN003 DRUG

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.

Part 1: Dose Level 1; Part 1: Dose Level 2; Part 1: Dose Level 3; Part 1: Dose Level 4; Part 2:ASLAN003 at Optinum Dose Level & Azacitidine; Part 2:ASLAN003 at Optinum Dose Level -1 & Azacitidine

Eligibility Criteria

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

You may qualify if:

• 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
• Patients who are able to understand and willing to sign the informed consent form (ICF)
• 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)
• 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.
• \. 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.
• \. 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

You may not qualify if:

• Patients who are diagnosed with de novo myeloid sarcoma without BM involvement
• Patients who are diagnosed with acute promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA)
• 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
• Patients with unresolved serious toxicity (≥ CTCAE 4.03 Grade 2) from prior administration of standard or investigational treatment for their leukemia
• 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
• Patients who have a known history of liver cirrhosis Child-Pugh score B or C
• Female patients who are pregnant or breast-feeding
• 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
• 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
• Patients who have been previously treated with ASLAN003

Sponsors & Collaborators

• ASLAN Pharmaceuticals: lead

Study Sites (8)

1 Site

Louisville, Kentucky, 40241, United States

Location

1 Site

Albury, New South Wales, Australia

Location

3 Sites

Darlinghurst, New South Wales, Australia

Location

1 Site

Waratah, New South Wales, Australia

Location

1 Site

Douglas, Queensland, Australia

Location

1 Site

Adelaide, South Australia, Australia

Location

3 Sites

Melbourne, Victoria, Australia

Location

3 Sites

Singapore, Singapore

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: ASLAN Pharmaceuticals

contact@aslanpharma.com

+65 6222 4235

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: March 1, 2018
• Study Start: January 5, 2018
• Primary Completion: September 11, 2019
• Study Completion: December 13, 2019
• Last Updated: July 6, 2021
• Results First Posted: July 2, 2021

Record last verified: 2021-07

Locations

US (1); AU (6); SG (1)