VICTOR: Venetoclax or Intensive Chemotherapy for Treatment Of Favourable Risk Acute Myeloid Leukaemia: a molecularly guided phase 2 study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The University Of Birmingham

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Jan 2025 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Cancer Research UK · AbbVie Ltd

External identifiers

EU CT number

2024-516116-19-00

EudraCT number

2020-000273-24

ISRCTN

ISRCTN15567173

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare molecular event free survival (mEFS) in AML patients receiving venetoclax and low dose cytarabine with those receiving intensive chemotherapy. mEFS is defined as;
1.Failure to achieve complete remission or complete remission with incomplete blood count recovery after two cycles of treatment
2.Molecular persistence (not responding to treatment), progression or relapse requiring treatment change
3.Morphological Relapse
4.Death

Secondary objectives 11

1. Occurrence of complete remission by the end of the second cycle of treatment
2. Death within 30 and 60 days from trial entry
3. Overall survival time
4. Time to haematological relapse
5. Time to molecular relapse
6. Cumulative occurrence of grade 3 and 4 toxicity
7. Prevalence of molecular complete remission at month 3, 6 and 12
8. Cumulative resource use at 12 and 24 months including hospital admission days, blood product usage and days on intravenous antibiotics and antifungals
9. Health related quality of life at month 3, 6, 12, 18 and 24
10. Change in performance status from baseline at month 3, 6, 12, 18 and 24
11. Change in Comprehensive Geriatric Assessment (CGA) from baseline at month 12 and 24

Conditions and MedDRA coding

Acute Myeloid Leukaemia

Regulatory references

Plan to share IPD

Yes

IPD plan description

The study data will be analysed at the CRCTU, University of Birmingham, by the trial bio-statisticians. Some biological data may be analysed by staff at Guys Hospital laboratory. Access to anonymised patient samples held at the Biobank at Guys Hospital may only be granted following ethical review of applications from research groups to the Biobank.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Diagnosis of CD33 positive Acute Myeloid Leukaemia
2. Age ≥55 years
3. Genotype NPM1mut FLT3 ITDneg (FLT3- Tyrosine Kinase Domain mutation, TKD, is permitted)
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
5. Serum creatinine ≤ 1.5 x ULN (upper limit of normal)
6. Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 ULN and bilirubin ≤ 2 x ULN
7. Able to provide written informed consent
8. Considered fit for intensive chemotherapy with anthracyclines by treating physician

Exclusion criteria 8

1. Previous chemotherapy for AML or any antecedent haematological condition, with the exception of hydroxycarbamide to control white blood cell count
2. Other active malignancy requiring treatment
3. Newly diagnosed or uncontrolled HIV or hepatitis B or C infection. Patients with known chronic infections may enrol if the last two tests for viral load have been negative and their current therapy does not include a protease inhibitor or a non-nucleoside reverse-transcriptase inhibitor
4. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry)
5. Females of childbearing potential, and their partners, not willing to use adequate contraception during and for up to 7 months after treatment
6. Unable to swallow tablets whole
7. Known hypersensitivity to any of the IMPs
8. Patients known to require vaccination with a live vaccine during the treatment period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Molecular event-free survival time (mEFS). An event is defined as follows: a) Failure to achieve morphological CR or CRi after two cycles of therapy, b) Molecular persistence, progression or relapse requiring treatment change (at any time), c) Morphological relapse (at any time) or d) Death (at any time)

Secondary endpoints 11

1. Occurrence of morphological complete remission (CR or CRi) by the end of the second cycle of treatment (see protocol section 8.14 for definitions of morphological response)
2. Death within 30 and 60 days from trial entry
3. Overall survival time
4. Time to morphological relapse (see protocol section 8.14 for definitions of morphological response)
5. Time to molecular relapse (see protocol section 8.14 for definitions of molecular response)
6. Cumulative occurrence of grade 3 and 4 adverse events at 12 and 24 months
7. Prevalence of molecular complete remission at month 3, 6 and 12
8. Cumulative resource use at 12 and 24 months including hospital admission days, blood product usage and days on intravenous antibiotics and antifungals
9. Health-related quality of life at month 3, 6, 12, 18 and 24
10. Change in performance status from baseline at month 3, 6, 12, 18 and 24
11. Change in Comprehensive Geriatric Assessment (CGA) from baseline at month 12 and 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The University Of Birmingham

Sponsor organisation

The University Of Birmingham

Address

Vincent Drive

City

Birmingham

Postcode

B15 2TT

Country

United Kingdom

Scientific contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Public contact point

Organisation

The University Of Birmingham

Contact name

Clinical Trial Coordinator

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications