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Trial registered on ANZCTR


Registration number
ACTRN12619000746134
Ethics application status
Approved
Date submitted
15/05/2019
Date registered
20/05/2019
Date last updated
7/07/2020
Date data sharing statement initially provided
20/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2 study of venetoclax in combination with low-dose cytarabine in relapsing acute myeloid leukemia
Scientific title
A phase 2 study of venetoclax in combination with low-dose cytarabine in relapsing acute myeloid leukemia
Secondary ID [1] 297664 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 311941 0
Condition category
Condition code
Cancer 310524 310524 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 313894 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319380 0
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
Timepoint [1] 319380 0
After 2 cycles of therapy
Secondary outcome [1] 367961 0
To assess the overall survival (OS) of patients via from hospital records and follow up
Timepoint [1] 367961 0
From day 1 of therapy until last date of follow-up (every 3 months for up to 3 years) or death.
Secondary outcome [2] 367966 0
Composite rate of clinical & laboratory tumor lysis syndrome (severity determined using Cairo-Bishop criteria) via laboratory blood tests
Timepoint [2] 367966 0
Upon reporting of adverse events at any point during the induction cycle.
Secondary outcome [3] 367968 0
To assess leukemia free survival (LFS) via from hospital records and follow up
Timepoint [3] 367968 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 13332 0
The Alfred - Prahran
Recruitment hospital [2] 13333 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 13336 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 15406 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 25933 0
3004 - Prahran
Recruitment postcode(s) [2] 25934 0
3128 - Box Hill
Recruitment postcode(s) [3] 25937 0
3000 - Melbourne
Recruitment postcode(s) [4] 28727 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 302193 0
Hospital
Name [1] 302193 0
Alfred Hospital
Address [1] 302193 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country [1] 302193 0
Australia
Primary sponsor type
Hospital
Name
Alfred Hospital
Address
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 302740 0
None
Name [1] 302740 0
Address [1] 302740 0
Country [1] 302740 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302873 0
Alfred Hospital Ethics Commitee
Ethics committee address [1] 302873 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Ethics committee country [1] 302873 0
Australia
Date submitted for ethics approval [1] 302873 0
03/04/2019
Approval date [1] 302873 0
16/09/2019
Ethics approval number [1] 302873 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91686 0
A/Prof Andrew Wei
Address 91686 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 91686 0
Australia
Phone 91686 0
+61 3 9076 2000
Fax 91686 0
Email 91686 0
a.wei@alfred.org.au
Contact person for public queries
Name 91687 0
Miss Flora Yuen
Address 91687 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 91687 0
Australia
Phone 91687 0
+61390765407
Fax 91687 0
Email 91687 0
flora.yuen@alfred.org.au
Contact person for scientific queries
Name 91688 0
A/Prof Andrew Wei
Address 91688 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 91688 0
Australia
Phone 91688 0
+61 3 9076 2000
Fax 91688 0
Email 91688 0
a.wei@alfred.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results