Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000994482p
Ethics application status
Not yet submitted
Date submitted
14/08/2025
Date registered
9/09/2025
Date last updated
9/09/2025
Date data sharing statement initially provided
9/09/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
ALLG AMLM28/A2 (ADAPT): Achieving Durable remissions via Adaptive Pro-survival Targeting in acute myeloid leukaemia (AML)) – VEN/AZA/Pelcitoclax. A therapeutic arm of the ALLG AMLM28 ADAPT Study-Master Protocol.
Scientific title
ALLG AMLM28/A2 (ADAPT): Achieving Durable remissions via Adaptive Pro-survival Targeting in acute myeloid leukaemia (AML)) – VEN/AZA/Pelcitoclax. A therapeutic arm of the ALLG AMLM28 ADAPT Study-Master Protocol.
Secondary ID [1] 314913 0
AMLM28/A2
Universal Trial Number (UTN)
Trial acronym
ADAPT/A2
Linked study record
This is an investigational combination treatment arm within the ALLG AMLM28 ADAPT trial platform, which is registered on ANZCTR with ID ACTRN12623000900617.

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 338232 0
Condition category
Condition code
Cancer 334509 334509 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is Pecitoclax. Pecitoclax is supplied as a lyophilized powder for injection (20mg/vial) to be reconstitute with 1.6 mL of water and further diluted with 0.9% sterile sodium chloride. It is administered through intravenous (IV) infusion for 30 minutes.

The patients enrolled into this therapeutic arm is part of the following domains from the ALLG AMLM28 ADAPT master protocol (ID ACTRN12623000900617):
Domain 1: AML with TP53 aberrations (ADAPT-TP53) or
Domain 2: AML with minimal residual disease (MRD) persistence (without TP53 aberrations) (ADAPT-MRD)

Safety run-in phase. 12 patients to be enrolled.
Pelcitoclax will be co-administered with standard of care treatment consisting of Venetoclax and Azacitidine on a 28 day cycle for 12 cycles:
-Azacitidine (75mg/m^2 per day) will be administered though IV from day 1 to day 5.
-Venetoclax (400mg) will be administered orally once a day from day 1 to day 21.
-Pelcitoclax will be administered on day 8, day 15, and day 22 at a starting dose of 240 mg IV.

Dose escalation and de-escalation of Pelcitoclax, part of the safety run-in phase, will be explored:
-Higher dose level:
1) 320 mg IV on Days 8, 15, and 22.
2) 320 mg IV on Days 1, 8, 15, and 22

-Lower dose levels:
1) 240 mg IV on Days 8 and 15 (omitting Day 22),
2)160 mg IV on Days 8 and 15

Dose Expansion Phase. Additional 38 patients enrolled.
Once the recommended dose is determined from the safety run-in, Pelcitoclax will continue to be administered with venetoclax and azacitidine on the same 28-day cycle for a total of 12 cycles:

Azacitidine: 75 mg/m² IV daily on Days 1–5
Venetoclax: 400 mg orally once daily on Days 1–21
Pelcitoclax: Dose and schedule as determined from safety run-in

All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance. Drug accountability is assessed through a combination of medical records, dispensing documentation, and physical review of returned medication packaging.
Intervention code [1] 331582 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 342473 0
Maximum tolerated dose of Pelcitoclax
Timepoint [1] 342473 0
Date of randomisation to day 28 of the treatment cycle
Primary outcome [2] 342474 0
Overall survival for patients from Domain 1: TP53 mutations
Timepoint [2] 342474 0
Date of randomisation to the date of death from any cause. Up to 3 years after treatment has stopped.
Primary outcome [3] 342475 0
Progression free survival (PFS) for patients from Domain 2: Persistent Minimal Residual Disease (MRD)
Timepoint [3] 342475 0
Date of randomisation to earliest date of progression (morphologic relapse) or date of death without prior progression, and up to 3 years after treatment has stopped.
Secondary outcome [1] 450960 0
Safety
Timepoint [1] 450960 0
Time from randomisation, continuous during treatment, and up to 3 years after treatment has stopped.
Secondary outcome [2] 450961 0
Tolerability
Timepoint [2] 450961 0
Time from randomisation, continuous during treatment, and up to 3 years after treatment has stopped.
Secondary outcome [3] 450962 0
Overall Survival for patients from Domain 2: MRD persistence
Timepoint [3] 450962 0
Date of randomisation to the date of death from any cause. Up to 3 years after treatment has stopped.
Secondary outcome [4] 450963 0
Treatment deliverability
Timepoint [4] 450963 0
Day 1 of one cycle to day 1 of next cycle) for the first 12 cycles of treatment
Secondary outcome [5] 450964 0
Event-Free Survival at 12-months
Timepoint [5] 450964 0
Measured from day 1 of registration to the date of treatment failure, hematologic relapse, or death from any cause, whichever occurs first.
Secondary outcome [6] 450965 0
Response
Timepoint [6] 450965 0
Baseline, day 28 of each cycle, 3 monthly follow up visits post treatment up to 24 months.
Secondary outcome [7] 450966 0
Relapse-Free Survival
Timepoint [7] 450966 0
Date of achievement of remission until the date of morphologic relapse or death from any cause up to 3 year after treatment has stopped.
Secondary outcome [8] 450967 0
Frequency of allogeneic stem cell transplant
Timepoint [8] 450967 0
From randomisation up to 3 year after treatment has stopped.
Secondary outcome [9] 450968 0
MRD Clearance
Timepoint [9] 450968 0
Day 28 of each cycle, 3 monthly follow up visits post treatment up to 24 months
Secondary outcome [10] 450970 0
TP53 mutation clearance
Timepoint [10] 450970 0
Day 28 of each cycle, 3 monthly follow up visits post treatment up to 24 months
Secondary outcome [11] 450972 0
Quality of life
Timepoint [11] 450972 0
At randomisation, day 1 of cycle 1, day 1 of cycle 2, day 1 of cycle 4, and day 1 of cycle 8.
Secondary outcome [12] 451735 0
Quality of life
Timepoint [12] 451735 0
At randomisation, day 1 of cycle 1, day 1 of cycle 2, day 1 of cycle 4, and day 1 of cycle 8.

Eligibility
Key inclusion criteria
A patient will be eligible for study participation in this treatment arm in domain 1 or 2 of the AMLM28 Platform trial (ACTRN12623000900617) if the patient meets the following criteria:
1. Meets inclusion/exclusion criteria outlined in the AMLM28 ADAPT Master Protocol (ACTRN12623000900617) .
2. A Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
3. Presence of either of the following criteria in patients undergoing frontline Acute Myeloid Leukaemia (AML) treatment with Venetoclax and Azacitidine (VEN-AZA):
a. Either mutated TP53, del17p or monosomy 17 at diagnosis. Patients eligible for this domain can enroll after completing 1-2 cycles of VEN-AZA (ADAPT-TP53), OR
b. Morphologic remission with less than 5% bone marrow (BM) blasts but persistently detectable measurable residual disease (MRD) equal or greater than 0.1% after completing at least 3 cycles of VEN-AZA by flow cytometry. Patients should commence study therapy within 180 days from AML diagnosis (ADAPT-MRD).
4. Adequate blood count parameters
a. For patients in ADAPT-TP53:
i. Platelet count equal or greater than 25 x109/L
b. For patients in ADAPT-MRD:
i. Platelet count equal or greater than 50 x109/L
ii. Neutrophils equal or greater than 0.5 x109/L
5. Adequate renal function as demonstrated by a creatinine clearance ?30 ml/min; calculated by the Cockroft Gault formula or measured by 24-hour urine collection.
6. Adequate liver function as demonstrated by :
a. Aspartate aminotransferase (AST) equal or less than 1.5 x Upper limit of Normal (ULN).
b. Alanine aminotransferase (ALT) equal or less than 1.5 x ULN.
c. Bilirubin equal or less than 1.5 xULN (unless considered due to Gilbert’s syndrome or AML).
7. Coagulation profile: APTT and PT equal or less than 1.5 x ULN.
8. Patient agrees to follow the recommended contraception procedures for this domain, see below:

Female patients must be either:
a) postmenopausal defined as:
i. Older than 55 years of age with no menses for 12 or more months without an alternative medical cause.
ii. 55 years of age or younger with no menses for 12 or more months without an alternative medical cause AND an FSH level over 40 IU/L.
OR
b) Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
OR
c) Woman of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control starting at day 1 through at least 180 days after the last dose of study drug.

Male patients who are sexually active, must agree, from day 1 through at least 180 days after the last dose of study drug, to practice the protocol specified Contraception outlined below. Male patients must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.

Females of childbearing potential must have negative results for pregnancy test performed:
a) At Screening with a serum sample obtained within 7 days prior to the first study drug administration, and
b) Patients with borderline pregnancy tests at Screening must have a serum pregnancy test equal or greater than 3 days later to document continued lack of a positive result.

While participating in this research study, female patients should not become pregnant or breastfeed a baby. Male patients should not father a baby.

Unless postmenopausal or permanently surgically sterile, a WOCBP must practice at least one of the following methods of birth control, on Study Day 1 (or earlier) through at least 180 days after the last dose of study drug.
a) Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) associated with the inhibition of ovulation, initiated at least 1 month prior to Study Day 1. Also, subjects must use a barrier method during this study from initial study drug administration to 180 days after the last dose of study drug.
b) Progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, initiated at least 1 month prior to Study Day 1. Also, patients must use a barrier method during this study from initial study drug administration to 180 days after the last dose of study drug.
c) Bilateral tubal occlusion/ligation or bilateral tubal occlusion via hysteroscopy (i.e., Essure), provided a hysterosalpingogram confirms success of the procedure.
d) Vasectomized partner(s), provided the vasectomized partner verbally confirms receipt of medical assessment of the surgical success, vasectomy occurred more than 3 months prior to screening, and is the sole sexual partner of the WOCBP trial participant.
e) Intrauterine device (IUD).
f) Intrauterine hormone-releasing system (IUS).
g) True abstinence: Refraining from heterosexual intercourse 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].

Male patients who are sexually active with a WOCBP, even if the male patients has undergone a successful vasectomy, must agree:
a) from Study Day 1 through at least 180 days after the last dose of study drug to use condoms and his female partner(s) must use at least one of the contraceptive measures (as defined in the protocol for female study patients of childbearing potential).
b) Additionally, male subject agrees not to donate sperm from Study Day 1 through at least 180 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
A patient will not be eligible for this treatment arm participation if any of the following criteria apply:
1. Presence of any general exclusion criteria outlined in the AMLM28 ADAPT Master Protocol (ACTRN12623000900617)
2. White Cell Count (WCC) greater than 15 x10^9/L. Hydroxyurea and/or thioguanine may be used for cytoreduction.
3. Active Central Nervous System (CNS) leukaemia.
4. The patient is unable to swallow tablets, or has malabsorptive issues that in the investigator’s opinion will interfere with absorption of study drugs.
5. 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: patients 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.
6. QT-interval corrected according to Fridericia’s formula (QTcf) >450ms.
7. Patient unable to have a 5-day washout prior to commencing first dose of study drug:
a. Strong or moderate cytochrome P450 (CYP)3A inducers such as Rifampin, carbamazepine, phenytoin and St John’s wort
b. Strong or moderate CYP3A inhibitors such as posaconazole, voriconazole, fluconazole, ketoconazole, clarithromycin, fosaprepitant, aprepitant. They are prohibited during cycle 1 of the safety run-in phase. At other times they may be used
if required with caution and with appropriate dose modifications for Venetoclax.
8. Patient unable to have a 3-day interval prior to the first dose of study drug from:
a. Grapefruit or grapefruit products, seville oranges (including marmalade containing Seville oranges), star fruit
9. Treatment with prior anti-leukemic therapy (not including VEN-AZA) within 14 days prior to the first dose of study drug.
10. History of other malignancy requiring active systemic treatment, or which is likely to result in an expected survival time of <2 years.
11. The patient is human immunodeficiency virus (HIV) positive.
12. Known hypersensitivity to the investigational agent.
13. The patient has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation.
14. Patient requiring medical treatment with antiplatelet or anticoagulants, or herbal supplement that affects platelet function within 7 days prior to the first dose of study drug.
15. Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or gated cardiac blood pool scan performed within 1 month prior to study entry results in a left ventricular ejection fraction that is equal or greater than 45%.
16. Patient has significant chronic respiratory disease that requires continuous oxygen.
17. Active bleeding or history of major bleeding (Grade 3+) within the last 12 months.

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
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
15/01/2029
Actual
Date of last data collection
Anticipated
15/01/2032
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 319478 0
Other Collaborative groups
Name [1] 319478 0
Australasian Leukaemia and Lymphoma Group
Country [1] 319478 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Country
Australia
Secondary sponsor category [1] 321966 0
None
Name [1] 321966 0
Address [1] 321966 0
Country [1] 321966 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 318048 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 318048 0
Ethics committee country [1] 318048 0
Australia
Date submitted for ethics approval [1] 318048 0
08/12/2025
Approval date [1] 318048 0
Ethics approval number [1] 318048 0

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

Contacts
Principal investigator
Name 142958 0
A/Prof Andrew Wei
Address 142958 0
Peter MacCallum Cancer Centre 305 Grattan St, Melbourne, Victoria 3000
Country 142958 0
Australia
Phone 142958 0
+61 3 9345 2555
Fax 142958 0
Email 142958 0
[email protected]
Contact person for public queries
Name 142959 0
Delaine Smith
Address 142959 0
Australasian Leukaemia & Lymphoma Group. 35 Elizabeth St Richmond Vic 3121
Country 142959 0
Australia
Phone 142959 0
+61 03 83739701
Fax 142959 0
Email 142959 0
[email protected]
Contact person for scientific queries
Name 142960 0
Delaine Smith
Address 142960 0
Australasian Leukaemia & Lymphoma Group. 35 Elizabeth St Richmond Vic 3121
Country 142960 0
Australia
Phone 142960 0
+61 03 83739701
Fax 142960 0
Email 142960 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

• Commercial organisations

Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
What individual participant data might be shared?
• De-identified individual participant data:
• All outcomes 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:
Data available 3 months following 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 catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]

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] Access can be requested via the Health Data Austra... [More Details]


Results publications and other study-related documents

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