Back to resultsA Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ASLAN003
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, ASLAN, DHODH
Eligibility Criteria
Inclusion Criteria:
- 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.
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:
- 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
- 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)
- 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
Sites / Locations
- 1 Site
- 1 Site
- 3 Sites
- 1 Site
- 1 Site
- 1 Site
- 3 Sites
- 3 Sites
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
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 -1 & Azacitidine
Part 2:ASLAN003 at Optinum Dose Level & Azacitidine
Arm Description
Outcomes
Primary Outcome Measures
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:
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
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))
Number of Participants With Adverse Events
Number of Participants with Adverse Events reported through 28 days post last study medication administration
Safety Assessments
Safety Assessments - Clinical laboratory test: Hematology and Chemistry
Secondary Outcome Measures
Relapse Free Survival
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. Relapse is defined as:
The reappearance of leukemic blasts in the peripheral blood or > 5% blasts in the bone marrow not attributable to any other cause;
The appearance of new dysplastic changes;
The reappearance of or development of cytologically proven extrameduallary disease;
The reappearance of a cytogenetic or molecular abnormality.
Clinical Benefit Rate
Defined as the proportion of subjects with an AML IWG best response of CR, CRi or PR. IWG Response Criteria in AML defines CR, CRi or PR as:
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
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))
Partial remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25 percent; and decrease of pre-treatment bone marrow blast percentage by at least 50 percent
% Change From Baseline in BM Blasts at Day 29
Percent Change from Baseline in BM Blasts at Day 29
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03451084
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
January 5, 2018 (Actual)
Primary Completion Date
September 11, 2019 (Actual)
Study Completion Date
December 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ASLAN Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
AML, ASLAN, DHODH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Dose Level 1
Arm Type
Experimental
Arm Title
Part 1: Dose Level 2
Arm Type
Experimental
Arm Title
Part 1: Dose Level 3
Arm Type
Experimental
Arm Title
Part 1: Dose Level 4
Arm Type
Experimental
Arm Title
Part 2:ASLAN003 at Optinum Dose Level -1 & Azacitidine
Arm Type
Experimental
Arm Title
Part 2:ASLAN003 at Optinum Dose Level & Azacitidine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
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.
Primary Outcome Measure Information:
Title
Overall Complete Remission Rate
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. IWG Response Criteria in AML defines CR or CRi as:
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
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))
Time Frame
4 months after study treatment
Title
Number of Participants With Adverse Events
Description
Number of Participants with Adverse Events reported through 28 days post last study medication administration
Time Frame
Through 28 days post last study medication administration
Title
Safety Assessments
Description
Safety Assessments - Clinical laboratory test: Hematology and Chemistry
Time Frame
Through 28 days post last study medication administration
Secondary Outcome Measure Information:
Title
Relapse Free Survival
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. Relapse is defined as:
The reappearance of leukemic blasts in the peripheral blood or > 5% blasts in the bone marrow not attributable to any other cause;
The appearance of new dysplastic changes;
The reappearance of or development of cytologically proven extrameduallary disease;
The reappearance of a cytogenetic or molecular abnormality.
Time Frame
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
Title
Clinical Benefit Rate
Description
Defined as the proportion of subjects with an AML IWG best response of CR, CRi or PR. IWG Response Criteria in AML defines CR, CRi or PR as:
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
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))
Partial remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25 percent; and decrease of pre-treatment bone marrow blast percentage by at least 50 percent
Time Frame
4 months after study treatment
Title
% Change From Baseline in BM Blasts at Day 29
Description
Percent Change from Baseline in BM Blasts at Day 29
Time Frame
Baseline and day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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:
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
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)
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
Facility Information:
Facility Name
1 Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40241
Country
United States
Facility Name
1 Site
City
Albury
State/Province
New South Wales
Country
Australia
Facility Name
3 Sites
City
Darlinghurst
State/Province
New South Wales
Country
Australia
Facility Name
1 Site
City
Waratah
State/Province
New South Wales
Country
Australia
Facility Name
1 Site
City
Douglas
State/Province
Queensland
Country
Australia
Facility Name
1 Site
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
3 Sites
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
3 Sites
City
Singapore
Country
Singapore
12. IPD Sharing Statement
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A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
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