Acute Myeloid LeukemiaPhase 2NCT03451084
A Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
A Phase 2 study testing ASLAN003 in people with Acute Myeloid Leukemia, run by ASLAN Pharmaceuticals at 8 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- ASLAN003
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 5 Jan 2018to 13 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
Australia6 sites
1 Site
Adelaide, South Australia
1 Site
Albury, New South Wales
3 Sites
Darlinghurst, New South Wales
1 Site
Douglas, Queensland
3 Sites
Melbourne, Victoria
1 Site
Waratah, New South Wales
About this study
Official title: A Phase IIA Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- ASLAN003
- Keywords
- AML, ASLAN, DHODH
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASLAN003Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose Level 1 | Experimental | Not described Receives: Drug: ASLAN003 |
| Part 1: Dose Level 2 | Experimental | Not described Receives: Drug: ASLAN003 |
| Part 1: Dose Level 3 | Experimental | Not described Receives: Drug: ASLAN003 |
| Part 1: Dose Level 4 | Experimental | Not described Receives: Drug: ASLAN003 |
| Part 2:ASLAN003 at Optinum Dose Level -1 & Azacitidine | Experimental | Not described Receives: Drug: ASLAN003 |
| Part 2:ASLAN003 at Optinum Dose Level & Azacitidine | Experimental | Not described Receives: Drug: ASLAN003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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))
Measured: 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
Measured: Through 28 days post last study medication administration
Safety Assessments
Safety Assessments - Clinical laboratory test: Hematology and Chemistry
Measured: Through 28 days post last study medication administration
Secondary outcomes (3)
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.
Measured: 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
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
Measured: 4 months after study treatment
% Change From Baseline in BM Blasts at Day 29
Percent Change from Baseline in BM Blasts at Day 29
Measured: Baseline and day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study start5 Jan 2018
- Primary completion11 Sep 2019
- Study completion13 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- ASLAN Pharmaceuticals
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03451084
- Sponsor's protocol ID
- ASLAN003-003
- Status last verified
- Jul 2021
- First submitted
- 23 Jan 2018
- Last updated
- 6 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIA Dose Optimisation Study of ASLAN003 in Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03451084
- Acronym / sponsor ID
- ASLAN003-003
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, ASLAN, DHODH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- ASLAN PharmaceuticalsUniversity, hospital or other
- Study start
- 5 Jan 2018 (actual)
- Primary completion
- 11 Sep 2019 (actual)
- Study completion
- 13 Dec 2019 (actual)
- First posted
- 1 Mar 2018 (actual)
- Results
- Posted 2 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASLAN003Patients 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. | Drug | 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 |
Primary outcome
Overall Complete Remission Rate
Time frame: 4 months after study treatment
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))
Number of Participants With Adverse Events
Time frame: Through 28 days post last study medication administration
Number of Participants with Adverse Events reported through 28 days post last study medication administration
Safety Assessments
Time frame: Through 28 days post last study medication administration
Safety Assessments - Clinical laboratory test: Hematology and Chemistry
3 secondary outcomes
Relapse Free Survival
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
Clinical Benefit Rate
Time frame: 4 months after study treatment
% Change From Baseline in BM Blasts at Day 29
Time frame: Baseline and day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ASLAN003 in people with Acute Myeloid Leukemia, run by ASLAN Pharmaceuticals at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Australia, United States, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Complete Remission Rate (time frame: 4 months after study treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2021.