Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625001003460p
Ethics application status
Not yet submitted
Date submitted
24/07/2025
Date registered
10/09/2025
Date last updated
10/09/2025
Date data sharing statement initially provided
10/09/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
ALLG AMLM29 CAVIAT-R (Chemotherapy and Venetoclax in Acute Myeloid Leukaemia (AML) Trial- Randomised): a multicentre phase III trial investigating venetoclax plus intensive chemotherapy for newly diagnosed AML
Scientific title
ALLG AMLM29 CAVIAT-R (Chemotherapy and Venetoclax in Acute Myeloid Leukaemia (AML) Trial- Randomised): a multicentre phase III trial investigating venetoclax plus intensive chemotherapy for newly diagnosed AML
Secondary ID [1] 314905 0
AMLM29
Universal Trial Number (UTN)
Trial acronym
CAVIAT-R (Chemotherapy and Venetoclax in AML Trial- Randomised
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 338214 0
Condition category
Condition code
Cancer 334492 334492 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is Venetoclax in combination with a reduced intensive chemotherapy regimen in induction and consolidation therapy. Venetoclax is supplied as an oral tablet, 100 mg. Venetoclax will be administered over a period of 9 days, with a single dose each day as specified.

Induction Treatment
For participants under 65 years:

Induction Cycle 1.
Day before the start of the main treatment: 100 mg of Venetoclax administered orally.
First day of main treatment: 200 mg of Venetoclax administered orally.
Days 1 to Day 7 of treatment period: 400 mg of Venetoclax administered orally once daily.
Chemotherapy:
Day 1 to Day 7 of treatment period: Ara-C (Cytarabine) 100 mg/m²/day will be administered with continuous intravenous infusion (CIV).
Day 1 to Day 3 of treatment period: Idarubicin 12 mg/m²/day will be administered as an intravenous (IV) bolus (administered 1 hour after Venetoclax dose).

For participants 65 years and older:

Day before the start of the main treatment: 200 mg of Venetoclax administered orally.
First day of main treatment: 400 mg of Venetoclax administered orally.
Days 1 to Day 7 of treatment period: 600 mg of Venetoclax administered orally once daily.
Chemotherapy:
Day 1 to Day 5 of treatment period: Ara-C (Cytarabine) 100 mg/m²/day will be administered CIV.
Day 2 to Day 3 of treatment period: Idarubicin 12 mg/m²/day administered as an IV bolus (administered 1 hour after Venetoclax dose).

Induction cycle 2 chemotherapy will be administered to patients with persistent disease (equal or greater than 5% Bone Marrow blasts) after 28 days of commencing induction cycle 1 treatment.
For participants under 65 years:

Days 1 to Day 7 of treatment period: Filgrastim 5mcg/kg daily administered subcutaneously (SC)
Day 2 to Day 6 of treatment period: Fludarabine 30mg/m^2 administered IV daily.
Day 2 to Day 6 of treatment period: Cytarabine administered IV 4 hours after Fludarabine administration. (Patients aged 60 years or younger will receive 2g/m^2 daily. Patients older than 60 years will receive 2g/m^2 daily)
Day 4 to Day 6 of treatment period: Idarubicin 8 mg/m^2 administered as an IV bolus daily.

For participants 65 years and older:
Day 1 to Day 3: Ara-C 1g/m^2 administered IV twice a day.

Consolidation Treatment will be administered to patients with less than 5% Bone Marrow blasts after 28 days of commencing induction treatment. Two cycles of treatment will be administered, with a 28 day gap between the cycles.
For participants under 65 years:

Days 1 to Day 7: 400 mg of Venetoclax administered orally once daily.
Chemotherapy:
Day 1 to Day 3: Ara-C (Cytarabine) 1.5g/m² twice a day administered IV.

For participants 65 years and older:

Days 1 to Day 7: 400 mg of Venetoclax administered orally once daily.
Chemotherapy:
Day 1 to Day 10: Low-dose cytarabine (LDAC) 20mg/m² is administered SC

All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.
Intervention code [1] 331509 0
Treatment: Drugs
Comparator / control treatment
The control treatment is Standard of Care (SOC) Chemotherapy:

Induction Cycle 1.
Day 1 to Day 7 of treatment period: Ara-C (Cytarabine): 200 mg/m²/day will be administered CIV.
Day 1 to Day 3.of treatment period: Idarubicin: 12 mg/m²/day administered as IV bolus.

Induction cycle 2 chemotherapy will be administered to patients with persistent disease (equal or greater than 5% Bone Marrow blasts) after 28 days of commencing induction cycle 1 treatment.
For participants under 65 years:

Days 1 to Day 7 of treatment period: Filgrastim 5mcg/kg daily administered subcutaneously (SC)
Day 2 to Day 6 of treatment period: Fludarabine 30mg/m^2 administered IV daily.
Day 2 to Day6 of treatment period: Cytarabine administered IV 4 hours after Fludarabine administration. (Patients aged 60 years or younger will receive 2g/m^2 daily. Patients older than 60 years will receive 2g/m^2 daily)
Day 4 to Day 6 of treatment period: Idarubicin 8 mg/m^2 administered as an IV bolus daily.

For participants 65 years and older:
Day 1 to Day 3: Ara-C 1g/m^2 administered IV twice a day.

Consolidation Treatment will be administered to patients with less than 5% Bone Marrow blasts after 28 days of commencing induction treatment. Two to four cycles of treatment will be administered, with a 28 day gap between the cycles, at the discretion of the investigator.

Day 1 to Day 3 treatment period: Ara-C (Cytarabine) will be administered IV twice a day. (Patients aged 60 years or younger will receive 1.5g/m^2. Patients older than 60 years will receive 1g/m^2.)

All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.
Control group
Active

Outcomes
Primary outcome [1] 342186 0
Event-Free Survival (EFS)
Timepoint [1] 342186 0
Day from randomisation to either failure to achieve complete remission (CR) by day 100 or to event. Assessments done at screening, day 28 after induction therapy, day 28 after consolidation therapy, and at time of suspected relapse. Until 5 years post treatment.
Primary outcome [2] 342187 0
Event Free survival (EFS)
Timepoint [2] 342187 0
Day from randomisation to either failure to achieve complete remission (CR) by day 100 or to event. Assessments done at screening, baseline, twice weekly during induction and consolidation therapy, end of cycle, and relapse assessment. Until 5 years post treatment.
Primary outcome [3] 342188 0
Event free survival (EFS)
Timepoint [3] 342188 0
Day from randomisation to either failure to achieve complete remission (CR) by day 100 or to event. Assessments done at screening, day 28 after induction therapy, day 28 after consolidation therapy, and at time of suspected relapse. Until 5 years post treatment.
Secondary outcome [1] 449855 0
Overall Survival (OS)
Timepoint [1] 449855 0
Time from randomisation to the date of death from any cause. Until 5 years post treatment.
Secondary outcome [2] 450241 0
Safety
Timepoint [2] 450241 0
Time from randomisation and continuous during treatment, at the 30 day safety visit until 5 years post treatment
Secondary outcome [3] 450243 0
Relapse-free survival
Timepoint [3] 450243 0
Day from randomisation to either failure to achieve complete remission (CR) by day 100 or to event. Assessments done at screening, day 28 after induction therapy, day 28 after consolidation therapy, and at time of suspected relapse. Until 5 years post treatment.
Secondary outcome [4] 450249 0
Additional disease response
Timepoint [4] 450249 0
ay from randomisation to either failure to achieve complete remission (CR) by day 100 or to event. Assessments done at screening, day 28 after induction therapy, day 28 after consolidation therapy, and at time of suspected relapse. Until 5 years post treatment.
Secondary outcome [5] 450250 0
Time to hematopoietic recovery
Timepoint [5] 450250 0
After induction and consolidation therapy.
Secondary outcome [6] 450251 0
Transplantation rate
Timepoint [6] 450251 0
From randomisation to date of transplant until 5 years post treatment
Secondary outcome [7] 450252 0
Post-consolidation therapy
Timepoint [7] 450252 0
After consolidation therapy until 5 years post treatment
Secondary outcome [8] 450949 0
Rate of transplant success
Timepoint [8] 450949 0
From randomisation to date of transplant until 5 years post treatment
Secondary outcome [9] 452028 0
rate of graft versus host disease (GVHD).
Timepoint [9] 452028 0
From randomisation to date of transplant until 5 years post treatment

Eligibility
Key inclusion criteria
1. Age 18 years and over.
2. Newly diagnosed AML (patients with core binding factor rearrangement and Acute Promyelocytic Leukaemia are excluded), with equal or greater than10% blasts, considered suitable for intensive chemotherapy.
3. Consented to the ALLG National Blood Cancer Registry (NBCR).
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 inclusive .
5. Adequate hepatic function as demonstrated by:
a. Bilirubin equal or less than 1.5x Upper limit of normal (ULN) (unless due to Gilbert’s syndrome or of non-hepatic origin), AND
b. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) equal or less than 3x ULN
unless considered to be due to leukaemic organ involvement.
6. Adequate renal function with calculated creatinine clearance greater than 30ml/min calculated by the Cockcroft Gault formula or measured by 24-hours urine at screening
7. Cardiac ejection fraction greater than 45% by echocardiogram (ECHO) or gated blood pool scan (GHPS).
8. No prior treatment for AML (Note: hydroxyurea, cytarabine (1-2 doses only), and/or thioguanine for cytoreduction is allowed).
9. White Cell Count (WCC) less than 25 x109/L (cytoreductive agents as specified above permitted for management of high WCC).
10. No contraindication to the use of the investigational product venetoclax.
11. Female patients must either be
a. Post-menopausal as defined by:
i. Age greater than 55 years with no menses for 12 or more months without an alternative medical cause OR
ii. Age equal or younger than 55 years with no menses for 12 or more months without an alternative medical cause AND an follicle stimulating hormone (FSH) level greater than 40 IU/L OR
1. Age 18 years and over.
2. Newly diagnosed AML (patients with core binding factor rearrangement and Acute Promyelocytic Leukaemia are excluded), with equal or greater than10% blasts, considered suitable for intensive chemotherapy.
3. Consented to the ALLG National Blood Cancer Registry (NBCR).
4. ECOG performance status 0-2 inclusive.
5. Adequate hepatic function as demonstrated by:
a. Bilirubin equal or less than1.5x ULN (unless due to Gilbert’s syndrome or of non-hepatic origin), AND
b. AST and ALT equal or less than 3x ULN
unless considered to be due to leukaemic organ involvement.
6. Adequate renal function with calculated creatinine clearance greater than 30ml/min calculated by the Cockcroft Gault formula or measured by 24-hours urine at screening
7. Cardiac ejection fraction greater than45% by echocardiogram (ECHO) or gated blood pool scan (GHPS).
8. No prior treatment for AML (Note: hydroxyurea, cytarabine (1-2 doses only), and/or thioguanine for cytoreduction is allowed).
9. White Cell Count (WCC) less than25 x109/L (cytoreductive agents as specified above permitted for management of high WCC).
10. No contraindication to the use of the investigational product venetoclax.
11. Female patients must either be
a. Post-menopausal as defined by:
i. Age greater than 55 years with no menses for 12 or more months without an alternative medical cause OR
ii. Age equal or younger than 55 years with no menses for 12 or more months without an alternative medical cause AND an follicle stimulating hormone (FSH) level greater than 40 IU/L OR
b. Women of childbearing potential (WOCBP) must use a highly effective method of contraception, and must not donate or cryopreserve eggs, from randomisation until 30 days after completion of trial protocol treatment. Highly effective methods include:
i. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
ii. Female sterilisation (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before randomisation . In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
iii. Male sterilisation (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
iv. Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate less than1%), for example hormone vaginal ring or transdermal hormone contraception.
12. Male patients who are sexually active with a WOCBP, even if the male patient has undergone a successful vasectomy, must agree from randomisation through at least 30 days after the last dose of trial protocol treatment to use condoms. Male patients must agree to refrain from sperm donation from randomisation through at least 30 days after the last dose of study drug.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Secondary AML with prior history of myeloproliferative neoplasm.
2. AML, post-cytotoxic therapy as defined by the World Health Organisation (WHO)2022 (cytotoxic therapy and/or large-field radiation therapy).
3. Evidence of central nervous system (CNS) leukaemia.
4. Prior treatment for AML (except for cytoreduction specified above) or prior exposure to Venetoclax or another BCL-2 inhibitor.
5. Prior treatment with a hypomethylating agent for myelodysplastic syndrome.
6. Unrelated malignancy with an expected survival of less than 3 years.
7. Evidence of cardiac, pulmonary, hepatic or renal disease, or clinically significant uncontrolled condition(s) including, but not limited to uncontrolled and/or active systemic infection (viral, bacterial or fungal) likely to affect tolerance to investigational therapy.
8. Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminated intravascular coagulation.
9. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
a. Clinically significant active systemic infection (viral, bacterial or fungal) requiring therapy.
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.
10. Patient has received the following within 7 days prior to the initial of study treatment
a. Strong or moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin and St John’s wort
11. Patient has received the following within 5 days prior to the initial study treatment
a. Strong or moderate CYP3A inhibitors such as posaconazole, voriconazole, fluconazole, ketoconazole, clarithromycin, fosaprepitant, aprepitant
12. Administration or consumption of any of the following within 3 days prior to the first dose of Venetoclax:
a. Grapefruit or grapefruit products, seville oranges (including marmalade containing Seville oranges), star fruit
13. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
14. Women who are pregnant or lactating.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation to either the IC-VEN arm or IC arm is conducted centrally by the trial coordinating centre (ALLG), following confirmation of eligibility and consent. Allocation is concealed until after registration, with randomisation details provided by the Clinical Research Associate (CRA) via secure communication. This process ensures that treatment allocation is not known to investigators or patients prior to enrolment, maintaining allocation concealment integrity.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be allocated to either IC or IC-VEN based on a 1:1 randomisation process created by computer software. The randomisation is stratified by age, with specific investigational regimens for patients younger than 65 years and 65 years or older and FLT3-mutation status.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/01/2026
Actual
Date of last participant enrolment
Anticipated
16/01/2030
Actual
Date of last data collection
Anticipated
17/01/2035
Actual
Sample size
Target
390
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 319466 0
Other Collaborative groups
Name [1] 319466 0
Australasian Leukaemia and Lymphoma Group
Country [1] 319466 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Country
Australia
Secondary sponsor category [1] 321956 0
Government body
Name [1] 321956 0
Australian Government Department of Health and Aged Care - Medical Research Future Fund (MRFF)
Address [1] 321956 0
Country [1] 321956 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 318040 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 318040 0
Ethics committee country [1] 318040 0
Australia
Date submitted for ethics approval [1] 318040 0
17/12/2025
Approval date [1] 318040 0
Ethics approval number [1] 318040 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142930 0
Prof Andrew Wei
Address 142930 0
Peter MacCallum Cancer Centre 305 Grattan St, Melbourne, Victoria 3000
Country 142930 0
Australia
Phone 142930 0
+61 3 9345 2555
Fax 142930 0
Email 142930 0
[email protected]
Contact person for public queries
Name 142931 0
Delaine Smith
Address 142931 0
ALLG 35 Elizabeth St Richmond Vic 3121
Country 142931 0
Australia
Phone 142931 0
+61 03 83739701
Fax 142931 0
Email 142931 0
[email protected]
Contact person for scientific queries
Name 142932 0
Delaine Smith
Address 142932 0
ALLG 35 Elizabeth St Richmond Vic 3121
Country 142932 0
Australia
Phone 142932 0
+61 03 83739701
Fax 142932 0
Email 142932 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
3 months after publication

To:
No end date
Where can requests to access individual participant data be made, or data be obtained directly?
• Data sharing request system: Health Data Australia

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  [email protected] ccess can be requested via the Health Data Austral... [More Details]


Results publications and other study-related documents

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