A phase 2 study of venetoclax in combination with low-dose cytarabine in relapsing acute myeloid leukemia

Phase 2

Recruiting

• Conditions: Acute Myeloid Leukemia; Cancer - Leukaemia - Acute leukaemia

• Registration Number: ACTRN12619000746134
• Lead Sponsor: Alfred Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-20
• Last Update Posted: 14 June 2021

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 32

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the efficacy of Venetoclax in combination with Cytarabine by the rate of remission or the detection of minimal residual disease which is assessed through review of bone marrow and peripheral blood examination and other medical record[After 2 cycles of therapy ]

Secondary Outcome Measures

Name	Time	Method
To assess the overall survival (OS) of patients via from hospital records and follow up[From day 1 of therapy until last date of follow-up (every 3 months for up to 3 years) or death.];Composite rate of clinical & laboratory tumor lysis syndrome (severity determined using Cairo-Bishop criteria) via laboratory blood tests[Upon reporting of adverse events at any point during the induction cycle.];To assess leukemia free survival (LFS) via from hospital records and follow up[From first clinical response until the last date of follow-up (every 3 months for up to 3 years) or the earlier of the dates of relapse or death]