None listed
Conditions
Brief summary
This is an investigational combination treatment arm within the ALLG AMLM26 INTERCEPT trial platform, which is registered on ANZCTR with ID ACTRN12621000439842. This treatment arm (PHI-101) will be evaluated for its activity in a population of participants with progressive acute myeloid leukemia (AML). Who is it for? You may be eligible for to receive this treatment if you are a part of the AMLM26 Intercept trial which is registered on ANZCTR with ID ACTRN12621000439842 (ie if you are aged 18 or older, you have been diagnosed with progressive acute myeloid leukemia, and are currently in your first or second morphologic remission with a known and trackable minimal residual disease (MRD) marker.). If you are on the AMLM26 Intercept trial you may be eligible for this treatment option if your disease is worsening. The trial management committee will review your disease characteristics and determine your best treatment option(s) available on the trial. Study details PHI-101 will be given orally at a dose of 160 mg on an empty stomach. It should be administered at least two hours after a meal, preferably following an overnight fast. After taking PHI-101, you must continue fasting for an additional two hours.PHI-101 will be administered on days 1-28 (every day) of each 28-day cycle. Participants will undergo a disease assessment at screening after cycle 1, cycle 2, cycle 3, cycle 6, cycle 8, cycle 10, cycle 12 and then 2 monthly until progression. This will require blood tests and bone marrow biopsies. Safety and tolerability of treatment will be assessed throughout the trial whilst you are receiving treatment. Health related quality of life during treatment will be assessed on the first treatment day of 3 consecutive cycles. This study is being carried out to improve the way we treat cancer patients who may have limited treatment options available to them. It is hoped that PHI-101 will be well tolerated and may improve outcomes for future patients, however, there may be no clear benefit from participation in this study.
Interventions
The ALLG AMLM26 INTERCEPT trial is an adaptive trial allowing the testing of multiple new therapeutic options targeting various AML biomarkers in a staged manner. The Master Protocol outlines the overall study structure (this is detailed in ANZCTR entry ACTRN12621000439842). There will be separate domains for each AML biomarker being investigated. Each domain will have at least one investigational agent. Each investigational agent may be used on its own and/or in combination with other agents. Each option will be a different treatment arm within a domain. Separate Therapy-Specific Protocol Appendices will include treatment-specific information for each investigational agent including all of the treatment arms specific to that investigational agent. Each treatment arm may be targeted to a specific AML biomarker (domain) and/or may be used when patients have no targetable option available. This entry is for the investigational monotherapy using PHI-101. PHI-101 is available in tablet form and will be administered orally once daily for up to 12 cycles, with each cycle lasting 28 days. The tablet should be taken on an empty stomach and must be administered at least two hours after a meal, preferably following an overnight fast. After taking the dose, participants must continue fasting for another two hours. Patients will enrol directly into a proof-of-concept (POC) phase, where the safety and efficacy of the recommended dose selected for expansion is 160mg once daily or days 1-28 of a 28-day cycle. No further dose exploration will be undertaken, as PHI-101 has previously been evaluated in a first-in-human, open-label phase 1a/1b trial (NCT04842370). That study included a dose-escalation phase ranging from 40 mg to 200 mg daily and identified 160 mg once daily as the recommended Phase 2 dose. This proposed arm aims to assess the safety, tolerability, and efficacy of PHI-101 in patients with FLT3-mutated AML who have experienced measurable residual disease (MRD) failure. Patients will be provided with a dosing schedule diary to complete at home. The pharmacy will perform drug accountability upon return of the empty bottles.
Sponsors
Australasian Leukaemia & Lymphoma Group
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient will be eligible for study participation to these PHI-101 treatment arm if he/she meets the following criteria: 1. Meets inclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol (ALLG AMLM26 INTERCEPT trial platform, which is registered on ANZCTR with ID ACTRN12621000439842) 2. ECOG 0-2 3. Subject must have adequate renal function as demonstrated by a creatinine clearance greater than 40 mL/min: calculated by the Cockcroft Gault formula or measured by 24-hours urine collection. 4. Subject must have adequate liver function as demonstrated by: a. aspartate aminotransferase (AST) less than 2.5 × ULN b. alanine aminotransferase (ALT) less than 2.5 × ULN c. bilirubin less than 1.5 × ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin) 5. Agrees to follow the recommended contraception procedures for this treatment domain
Exclusion criteria
A subject will not be eligible for participation on these PHI-101-containing treatment arms if any of the following criteria apply: 1. Presence of any general exclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol (ALLG AMLM26 INTERCEPT trial platform, which is registered on ANZCTR with ID ACTRN12621000439842) 2. Prior allogeneic stem cell transplantation within 30 days of stem cell infusion or has clinically significant graft-versus-host disease requiring treatment, or has persistent greater than or equal to grade 2 non-haematologic toxicity related to transplant 3. QT-interval corrected according to Fridericia’s formula (QTcF) greather than 450ms (except for right bundle branch block) 4. Presence of hypokalemia (defined as serum potassium less than 3.5 mmol/L) and hypomagnesaemia (defined as serum magnesium less than 0.7 mmol/L) at the time of screening for this treatment arm. Supplementation is permitted during the screening window to establish values above the defined thresholds above. 5. Subject is HIV positive 6. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal) b. Acute/Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) or resolved HBV infection may participate. 7. Chronic systemic chronic corticosteroid therapy (greater than or equal to 10 mg/day prednisone or equivalent) or any immunosuppressive therapy within the last 7 days prior to Day 1 of study drug. Topical, inhaled, nasal and ophthalmic steroids are allowed. 8. History of or current drug-induced interstitial lung disease or pneumonitis 9. Subject has been diagnosed with another malignancy, unless disease-free for at least 2 years and not needing active treatment. Patients with fully excised BCC/SCC/CIN or other minor malignancy are not excluded 10. Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation 11. Use of any live vaccines against infectious diseases (i.e. Influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment 12. Impaired cardiac function or clinically significant cardiac disease, including any of the following: • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade greater than or equal to 2) with an LVEF of less than 45%, uncontrolled hypertension or clinically significant arrhythmia • Acute myocardial infarction or unstable angina pectoris less than 3 months prior to study entry 13. Use of medications, herbal products or foods known to be moderate or potent inhibitors of P glycoprotein (P-gp) within the last 7 days prior to Day 1 or known to be moderate or potent inducers of P-gp within the last 14 days prior to Day 1 14. Patients unable to swallow oral medications, or with gastrointestinal issues which might affect oral drug absorption or ingestion (i.e, gastroparesis, etc). 15. Prior treatment with cytotoxic/anti-leukaemic agents (apart from hydroxyurea, thioguanine, or single dose of cytarabine infusion for control of leucocytosis) within 2 weeks prior to first dose of study agent, or within 5 half-lives prior to study drug administration.
Outcome results
None listed