None listed
Conditions
Brief summary
This is an investigational agent within the ALLG AMLM26 INTERCEPT trial platform, which is registered on ANZCTR with ID ACTRN12621000439842. This investigational agent (SNDX5613- a new treatment) will be evaluated for its activity alone 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 SNDX5613 is given orally by itself twice daily on an empty stomach at least 2hrs after a meal or 1 hour before the next meal. Administered days 1-28 of a 28 day cycle for 12 cycles. Patients with minimal residual disease will have a pilot safety run-in phase to confirm dose - investigating doses 276mg twice daily, 226mg twice daily and 163mg twice daily. Once a tolerable dose is determined that dose will be used in a proof of concept phase.. Patients with morphologic relapse will enter directly into a proof of concept phase using 276mg twice daily dose. Participants will undergo a disease assessment at screening after cycle 1, cycle 2, cycle 3, cycle 6 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 SNDX5613 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 agent SNDX5613. This will have 1 treatment arm - SNDX5613 alone. SNDX5613 is a capsule that will be administered orally twice a day. Taken on an empty stomach at least 2 hours after a meal or 1 hour before the next meal. Administered days 1-28 of a 28 days cycle for 12 cycles. As this agent has not yet been tested in patients with MRD progression, we will confirm the dose for patients with MRD progression in a pilot safety run-in phase. The first dose level explored will be 276mg twice a day. If not tolerable 226mg twice a day will be investigated, and if that is not tolerable 163mg twice a day will be investigated. Once the optimal dose is determined in the pilot phase for MRD progressors, enrolment onto a proof of concept phase will commence using the dose level deemed tolerable. Patients in the morphologic relapse will immediately be enrolled into the POC phase at a dose of 276mg twice a day SNDX-5613 from days 1-28 of a 28-day cycle (utilising the recommended phase 2 dose determined by the SNDX- 5613 sponsored phase 1b/II study (NCT04065399) to be most tolerable and effective). Patients will be asked to complete a dose diary to confirm the tablets were taken. Patients will also be asked to return the SNDX5613 bottles (with unused tablets or empty containers) to the hospital. This is to monitor compliance with the treatment.
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
1. Meets inclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol (see ACTRN12621000439842 for details on the master protocol) 2. Presence of MLL-r, NPM1, UBTF-TD, DEK::NUP214, NUP98r, MLL-PTD mutations or other aberrant HOX expressing AML subsets confirmed by the MRC, in a bone marrow or peripheral blood sample taken no more than 42 days prior to cycle 1 of day 1 of treatment on this treatment arm. Patients withMLL-r with mixed-phenotype acute leukaemia (MPAL) will also be considered eligible for this study 3. ECOG 0-2 4. Confirmation of serum potassium greater than or equal to 3.6 mmol/L and serum magnesium greater than or equal to 0.66 mmol/L within one week before first dose of study drug, at which time oral supplementation can be started to maintain potassium greater than or equal to 4.0 and magnesium greater than or equal to 0.82 to meet electrolyte thresholds for SNDX5613 dosing. 5. Subject must have adequate renal function as demonstrated by a creatinine clearance greater than or equal to 60 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection 6. Adequate cardiac function defined as left ventricular ejection fraction (EF) of greater than 50% by echocardiogram or multi-gated acquisition (MUGA) scan. 7. Subject must have adequate liver function as demonstrated by: a. aspartate aminotransferase (AST) less than or equal to 3.0 × ULN b. alanine aminotransferase (ALT) less than or equal to 3.0 × ULN c. bilirubin less than or equal to 1.5 × ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non- hepatic origin) 8. Agrees to follow the recommended contraception procedures for this treatment arm
Exclusion criteria
1. Presence of any general exclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol (see ACTRN12621000439842 for details on the master protocol) 2. QT-interval corrected according to Fridericia’s formula (QTcF) greater than 450ms on triplicate ECGs (each separated by 2 minutes with average of 3 ECGs used to calculate QTcF interval). 3. Subject is HIV positive and has detectable HIV viral PCR and/or with signs of active/uncontrolled infection. Patients who are HIV-positive with undetectable viral load are eligible provided that anti-retroviral used is not a prohibited medication on study. 4. Prior allogeneic stem cell transplantation within 60 days of stem cell infusion. 5. Prior donor lymphocyte infusion within 4 weeks of cycle 1 day 1. 6. Systemic immunosuppressive therapy or >10mg/day prednisolone for graft vs host disease (GVHD). Patients must have been off systemic immunosuppressive therapy (apart from stated prednisolone dose above) for the purposes of GVHD for at least 4 weeks prior to enrolment. 7. 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. 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 patients who have past exposure to HepB (HepB Surface Antigen negative but core antibody positive and DNA negative) who do not require treatment may participate. 8. Patients who have ingested seville oranges, grapefruit or grapefruit juice and/or kumquats, pomegranate or pomegranate juice, pomelos, exotic citrus fruit (i.e., star fruit, bitter melon), grapefruit hybrids or fruit juices, or other foods and juices known to inhibit CYP3A4 within three days prior to initiation of study treatment, and are not willing to cease their ingestion for the duration of the study. 9. Treatment with any of the following within 7 days prior to the first dose of study drug: a. Steroid therapy for anti-neoplastic intent or on greater than 10mg/day prednisolone for graft versus host disease b. Moderate or strong CYP3A inducers c. CYP3A inhibitors: • SAFETY RUN-IN PHASE PATIENTS: Moderate and strong cytochrome CYP3A inhibitors are prohibited 7 days prior to cycle 1 day 1 and during cycle 1 of the safety run-in phase. • PROOF OF CONCEPT (POC) AND EXPANSION PHASE PATIENTS: Moderate and strong cytochrome CYP3A4 inhibitors with the exception of posaconazole, voriconazole, itraconazole or ketoconazole are prohibited 7 days prior to cycle 1 day 1. Patients on azole antifungals should have been on it for greater than or equal to 7 days prior to first dose of SNDX-5613. 10. Treatment with prior anti-leukemic therapy within 5 half-lives or 14 days (whichever is shorter) prior to the first dose of study drug (except steroids see exclusion 7a). 11. 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. 12. Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation 13. Subject has had any of the following within 6 months prior to screening: myocardial infarction, uncontrolled/unstable angina, congestive heart failure New York Heart Association (NYHA) class 3 or 4, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. 14. Patients unable to swallow oral medications, or with gastrointestinal issues which might affect oral drug absorption or ingestion (i.e, gastroparesis, etc).
Outcome results
None listed