None listed
Conditions
Brief summary
The purpose of this study is to determine whether Venetoclax (a new drug), when combined with chemotherapy, improves response to treatment. Who is it for? You may be eligible to participate in this trial if you are aged 18 years or over, have been diagnosed with relapsed acute myeloid leukemia Study Details Eligible participants will receive venetoclax in combination with low-dose cytarabine. Treatment (each cycle is 28 days) will be given until disease progression, unacceptable toxicity, or withdrawal of consent. Participants will be required to have blood samples taken at the beginning of each cycle along with a medical exam in order for researchers to monitor whether the treatment is safe and whether it is effectively treating the leukemia. It is hoped that the findings of this trial will establish the benefits of venetoclax in combination with cytarabine for the treatment of leukemia patients early in the course of their disease.
Interventions
All patients will will be administered Venetoclax orally once daily (QD) Days 1 through 28, of a 28-day cycle, with a designated dose of 600 mg daily.
Cytarabine (20 mg/m2) will be administered by subcutaneous injection be given QD following administration of Venetoclax on Days 1-10 of every cycle.
Patients will remain on treatment for up to 24 cycles unless discontinuation criteria is met.
Adherence is monitored through hospital drug administration records and tablet adherence through drug p
All patients will will be administered Venetoclax orally once daily (QD) Days 1 through 28, of a 28-day cycle, with a designated dose of 600 mg daily. Cytarabine (20 mg/m2) will be administered by subcutaneous injection be given QD following administration of Venetoclax on Days 1-10 of every cycle. Patients will remain on treatment for up to 24 cycles unless discontinuation criteria is met. Adherence is monitored through hospital drug administration records and tablet adherence through drug packet return.
Sponsors
Alfred Hospital
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. Relapsing AML 2. Received no more than 1 prior line of intensive chemotherapy for AML a. Post-remission therapy incl. consolidation, maintenance or HSCT is considered 1 line of therapy b. Prior hypomethylating agent is permitted 3. Age 18 years or older. No upper age limits. 4. ECOG performance status 0-2 5. Adequate organ function as defined by: a. Creatinine clearance equal to or greater than 30 ml/min b. Bilirubin less than or equal to 1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin) c. Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3.0 x ULN 6. WCC <25 x 109/L (hydroxyurea or thioguanine are permitted to meet this criterion) 7. Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and for 30 days following the date of last dose
Exclusion criteria
1. Acute promyelocytic leukemia 2. Prior and concomitant therapy a. Anticancer therapies including chemotherapy, radiotherapy, or other investigational therapy, including targeted small molecule agents: exclude 5 half-lives prior to first dose and throughout venetoclax administration b. Biologic agents (e.g. monoclonal antibodies) for anti-neoplastic intent: exclude 30 days prior to first dose and throughout venetoclax administration 3. Prior exposure to Venetoclax or other BCL-2 inhibitors 4. Known contraindication of or allergy to allopurinol, xanthine oxidase inhibitors and rasburicase 5. History of malignancy with the exception of: a. Adequately treated in situ carcinoma of the cervix uteri b. Adequately treated non-melanoma skin cancer c. Localized prostate cancer with no requirement for therapy d. Prior cancer not requiring active therapy and with an expected survival greater than 2 years 6. Subject is known to be positive for HIV (HIV testing is not required) 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) may participate 8. Treatment with any of the following within 7 days prior to the first dose of study drug: a. Steroid therapy for anti-neoplastic intent b. Moderate or strong CYP3A inhibitors c. Moderate or strong CYP3A inducers 9. Administration or consumption of any of the following within 3 days prior to the first dose of study drug: a. Grapefruit or grapefruit products b. Seville oranges (including marmalade containing Seville oranges) c. Star fruit 10. Significant medical, psychiatric, or any other condition that in the opinion of the investigator would adversely affect subject’s participation in this study or interpretation of study results
Outcome results
None listed