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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05005299




Registration number
NCT05005299
Ethics application status
Date submitted
8/08/2021
Date registered
13/08/2021
Date last updated
1/08/2023

Titles & IDs
Public title
Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation
Scientific title
The VICTORY Study: A Phase I Study of Venetoclax in Combination With Non-myeloablative Conditioning Allogeneic Haematopoietic Stem Cell Transplantation
Secondary ID [1] 0 0
2021.238
Universal Trial Number (UTN)
Trial acronym
VICTORY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Myeloid, Acute 0 0
Leukemia, Lymphoblastic, Acute, L1 0 0
Leukemia, Lymphoblastic, Acute, L2 0 0
Myelodysplastic Syndromes 0 0
Non-hodgkin Lymphoma 0 0
Plasma Cell Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Blood 0 0 0 0
Haematological diseases
Cancer 0 0 0 0
Other cancer types
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - Fludarabine
Treatment: Drugs - Cyclophosphamide

Experimental: Dose Level A - Subjects will receive receive short-course venetoclax on day -11 to -6 [venetoclax 100mg daily administered on day -11 to -6 (total venetoclax dose: 600mg)], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Experimental: Dose Level B - Subjects will receive receive short-course venetoclax on day -11 to -6 [venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 to -6 (total venetoclax dose: 1100mg)], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Experimental: Dose Level C - Subjects will receive receive short-course venetoclax on day -11 to -6 [venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10, 400mg daily administered on day -9 and 600mg daily administered on day -8 to -6 (total venetoclax dose: 2500mg)], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.

Experimental: Dose Level B' - Subjects will receive receive short-course venetoclax on day -11 to -6 [venetoclax 100mg daily administered on day -11, followed by 200mg daily administered on day -10 and 400mg daily administered on day -9 to -6 (total venetoclax dose: 1900mg)], followed by intravenous fludarabine 30mg/m2 daily (day -5 to -3) and intravenous cyclophosphamide 750mg/m2 daily (day -5 to -3). Allogeneic stem cell infusion will occur on day 0.


Treatment: Drugs: Venetoclax
Venetoclax is administered as an oral tablet once daily.

Treatment: Drugs: Fludarabine
Fludarabine is administered as an intravenous infusion at a dose of 30mg/m2 daily, to be administered over 30 minutes.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide is administered as an intravenous infusion at a dose of 750mg/m2 daily, to be administered over 30 minutes and to commence 1 hour after fludarabine infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The development of any dose-limiting toxicities
Timepoint [1] 0 0
Time point between time of first dose of venetoclax to day 30 post-alloSCT
Secondary outcome [1] 0 0
Acute GVHD incidence and severity
Timepoint [1] 0 0
180 days post allo-SCT
Secondary outcome [2] 0 0
Chronic GVHD incidence and severity
Timepoint [2] 0 0
1-year post-alloSCT
Secondary outcome [3] 0 0
GVHD, relapse-free survival (GRFS) incidence
Timepoint [3] 0 0
1-year post-alloSCT
Secondary outcome [4] 0 0
Relapse and non-relapse mortality incidence
Timepoint [4] 0 0
1-year post-alloSCT
Secondary outcome [5] 0 0
Donor/recipient chimerism
Timepoint [5] 0 0
Measured at days 30, 60, 100, 1 year and 2 years following alloSCT

Eligibility
Key inclusion criteria
Patients are eligible for inclusion if all of the following criteria are met:

- Age = 18 years

- Planned to undergo alloSCT for one of the following haematological malignancies: acute
leukaemia (including myeloid and/or lymphoid lineage or biphenotypic), myelodysplastic
syndrome, chronic lymphocytic leukaemia (CLL), B-cell non-Hodgkin lymphoma (NHL) and
plasma cell myeloma

- Physician preference for a non-myeloablative conditioning regimen

- Available 10/10 HLA-matched related or unrelated haematopoietic stem cell donor

- Transplantation to be performed from a peripheral blood stem cell source

- Adequate renal and hepatic function at screening as follows:

1. Calculated creatinine clearance >50ml/min as measured by Cockroft Gault formula

2. AST and ALT = 3.0 x ULN

3. Bilirubin = 1.5 x ULN (except patients with Gilbert's Syndrome)

- Able to tolerate oral medications

- Disease status at the time of transplantation as follows:

1. Acute leukaemia in complete morphologic remission

2. Myelodysplastic syndrome with less than 10% bone marrow blasts

3. CLL in complete remission (CR), partial response (PR) or PR with lymphocytosis

4. NHL in CR or PR

5. Myeloma in CR, very good partial response (VGPR) or PR within 3 months of prior
autologous stem cell transplantation as part of a tandem auto-allo transplant
approach

- ECOG performance status 0-1
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from this study if any of the following criteria are met:

- Moderate or high risk of tumour lysis syndrome prior to conditioning for allogeneic
transplantation, defined as:

1. For CLL: Diameter of any lymph node or tumour mass >5cm OR absolute lymphocyte
count=25x10^9/L

2. For NHL: Diameter of any lymph node or tumour mass >5cm

- Prior intolerance of venetoclax or another BCL-2 inhibitor with the exception of
cytopenias. Patients with prior clinical tumour lysis syndrome following venetoclax or
other BCL-2 inhibitor will be excluded from the study if at the time of prior TLS
their disease burden was as follows:

1. For CLL: Diameter of any lymph node or tumour mass <5cm OR absolute lymphocyte
count=25x10^9/L

2. For NHL: Diameter of any lymph node or tumour mass <5cm

- Reticulin fibrosis of the marrow of grade MF 2-3

- Prior allogeneic stem cell transplantation

- Haemopoietic cell transplantation - comorbidity index (HCT-CI) score > 5

- Any currently active malignancy other than the primary indication for alloSCT (except
localized basal cell carcinoma or squamous cell carcinoma of the skin)

- Uncontrolled systemic infection

- Known malabsorption syndrome

- Has received within 7 days prior to the first dose of venetoclax CYP3A4 inducers such
as rifampicin, carbamazepine, phenytoin and St John's wort

- Has received within 7 days prior to the first dose of venetoclax CYP3A4 inhibitors

- Known positivity to HIV

- Significant physical or psychiatric comorbid illness that in the investigator's
opinion would impair the patient's ability to participate in the study.

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2026
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Melbourne Health - Melbourne
Recruitment postcode(s) [1] 0 0
3050 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Melbourne Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1, open-label, single center study of short-course oral venetoclax therapy
prior to non-myeloablative conditioning with fludarabine and cyclophosphamide in subjects
with haematological malignancies who are planned for allogeneic stem cell transplantation
(alloSCT). The primary study objective is to determine the safety and maximum tolerated dose
of venetoclax when used in combination with fludarabine and cyclophosphamide conditioning.
Secondary objectives were to evaluate the transplant outcomes and donor/recipient engraftment
of this regimen.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05005299
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Ritchie
Address 0 0
Melbourne Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Ritchie
Address 0 0
Country 0 0
Phone 0 0
+61393427000
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05005299