None listed
Conditions
Brief summary
This study aims to explore the safety of BYT-1007 and BYT-1007/venetoclax combination and their potential to treat certain blood cancers. Who is it for? You may be eligible for this study if you are male or female, aged 18 to 74. To be eligible for Part A you must be diagnosed with specific hematologic malignancies such as acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and high-risk myelodysplastic syndromes (HR-MDS), either in relapsed/refractory status or, in some cases, treatment-naive but unfit for intensive chemotherapy. To be eligible for Part B you must only be diagnosed with acute myeloid leukaemia (AML). Participants must also be unsuitable for standard intensive treatment and have adequate organ function, including kidney function (creatinine clearance of at least 30 mL/min), liver function within the study-specified limits, and a white blood cell count below 25 billion cells/L (supportive treatment may be used to achieve this threshold). Study details Part A will evaluate increasing dose levels of BYT-1007 given alone. Participants will be enrolled sequentially into dose-escalation cohorts and receive five doses of BYT-1007 during a 28-day treatment period. Information collected from Part A will help determine the most appropriate dose for further evaluation. Part B will evaluate BYT-1007 given together with venetoclax. Participants will receive BYT-1007 at dose levels determined based on the results from Part A, in combination with venetoclax during a 28-day treatment period. Participants will attend regular study visits and undergo blood tests, bone marrow assessments, physical examinations, and other safety evaluations to monitor their health and response to treatment. It is hoped that the results of this study will help determine whether BYT-1007, alone or in combination with venetoclax, may be further developed as a potential treatment option for patients with blood cancers, particularly AML.
Interventions
Part A (BYT-1007 monotherapy)
Participants will be enrolled sequentially into escalating dose cohorts. Dose levels will be assessed sequentially rather than concurrently. After all participants within a dose cohort complete Cycle 1 (the dose-limiting toxicity [DLT] evaluation period), the Safety Review Committee (SRC) will review the available safety data and determine whether dose escalation to the next cohort may proceed.
The planned dose levels of BYT-1007 are 5 mg/day, 10 mg/day, 15 mg/day,
Part A (BYT-1007 monotherapy) Participants will be enrolled sequentially into escalating dose cohorts. Dose levels will be assessed sequentially rather than concurrently. After all participants within a dose cohort complete Cycle 1 (the dose-limiting toxicity [DLT] evaluation period), the Safety Review Committee (SRC) will review the available safety data and determine whether dose escalation to the next cohort may proceed. The planned dose levels of BYT-1007 are 5 mg/day, 10 mg/day, 15 mg/day, and 25 mg/day, with 40 mg/day as an optional dose. The actual dose escalation may be modified based on safety findings and recommendations from the Safety Review Committee (SRC). BYT-1007 will be administered orally as capsules. The planned treatment duration is one 28-day cycle, with up to three additional 28-day cycles permitted at the Investigator's discretion. Treatment adherence will be monitored through direct administration and observation during the mandatory hospitalization period (Day 1 to Day 7), together with study drug accountability records, dosing records, and returned unused study medication (if applicable). --- Part B (BYT-1007 + venetoclax combination therapy) Part B will commence after the maximum tolerated dose (MTD) of BYT-1007 monotherapy has been determined and reviewed by the Safety Review Committee (SRC). Participants enrolled in Part A may be eligible for enrolment into Part B if they meet all Part B eligibility criteria and provide informed consent. Participants will be enrolled sequentially into the currently open dose cohort according to the study dose-escalation scheme. The starting dose of BYT-1007 in Part B will be one dose level below the maximum tolerated dose (MTD) established during Part A. The maximum dose level evaluated will not exceed the MTD established in Part A and is expected to be no higher than 40 mg/day. The dose of venetoclax will be fixed at its recommended dosage for AML (Days 1-3 of Cycle 1: 100-200-400 mg/day dose ramp-up; Cycle 1 Day 4 and beyond: 400 mg/day). BYT-1007 will be administered orally as capsules, and venetoclax will be administered orally as tablets. The planned treatment duration is one 28-day cycle, with up to three additional 28-day cycles permitted at the Investigator's discretion. Treatment adherence will be monitored through inpatient administration during the mandatory hospitalization period (Day 1 to Day 7), study drug accountability records, dosing records, and returned unused study medication (if applicable).
Sponsors
Boyen Therapeutics Australia Pty Ltd
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 74 Years
Healthy volunteers
No
Inclusion criteria
An eligible participant must fulfill all of the following inclusion criteria: 1. Participants with one of the following histologically/cytologically confirmed hematologic malignancies: Part A: ALL in relapsed/refractory status Primary or secondary AML in relapsed/refractory status Primary or secondary HR-MDS according to IPSS/IPSS-R/IPSS-M criteria in relapsed/refractory status Any above-mentioned hematologic malignancy in treatment-naïve status but not eligible for intensive induction chemotherapies due to age or lack of fitness (prior hydroxyurea treatment is allowed) Part B: primary or secondary AML in relapsed/refractory status or in treatment-naïve status but not eligible for intensive induction chemotherapies 2. Adequate renal and hepatic function, defined as Estimated creatinine clearance of at least 30 mL/min, calculated using the Cockcroft-Gault formula or measured by 24-hour urine collection. Serum bilirubin no greater than 1.5 times the upper limit of normal (ULN). Serum bilirubin no greater than 3.0 times the upper limit of normal (ULN) for treatment-naïve participants between 18 to 74 years of age. Aspartate transaminase (AST) and alanine transaminase (ALT) no greater than 3.0 times the upper limit of normal (ULN). 3. White blood cell count less than 25 billion cells/L (hydroxyurea administration or leukapheresis is permitted to meet this criterion). 4. ECOG Performance Status 0 to 2 OR 2 to 3 for treatment naïve participants between 18 to 74 years of age 5. Women of childbearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use protocol specified highly effective contraceptive methods from Cycle 1 Day 1 through at least 180 days after the last dose of study drug, and must have a negative serum pregnancy test within 2 weeks prior to Cycle 1 Day 1 6. Sexually active male must agree to practice protocol-specified methods of contraception and refrain from sperm donation from Cycle 1 Day 1 through at least 180 days after the last dose of study drug. 7. Must be able and willing to give written informed consent.
Exclusion criteria
Any patient who has any of the following exclusion criteria: 1. Acute promyelocytic leukemia 2. CNS involvement 3. Life expectancy <12 weeks 4. Having received major surgical procedures or investigational products within 4 weeks, or anticancer therapies within 2 weeks (prior hydroxyurea treatment is allowed) 5. Currently participating in other clinical studies 6. Known HIV infection 7. Known active HBV/HCV infection. Inactive hepatitis carrier status or low viral hepatitis titer (HBV viral DNA < 2,000 IU/mL; HCV viral RNA< 50 genome equivalents/mL) on antivirals (non-exclusionary medications) are not excluded. 8. Concurrent history of active malignancy in past two years, with the exception of Adequately treated in situ carcinoma of the cervix uteri or breast; Basal cell or localized squamous cell carcinoma of the skin; Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. 9. Concurrent severe and/or uncontrolled medical condition (e.g., uncontrolled diabetes, infection, hypertension, pulmonary disease), which in the Investigator's opinion could compromise the patient's safety 10. Swallowing difficulties or other condition that precludes oral route of administration 11. Being allergic to the active ingredient or any excipient of BYT-1007 or (Part B only) venetoclax 12. Previous treatment with clofarabine or (Part B only) venetoclax 13. Received prohibited medication/food within the specified timeframe prior to Cycle 1 Day 1 14. Pregnant or lactating females 15. Unwilling or not capable of using effective means of contraception
Outcome results
None listed