Venetoclax as treatment of acute graft-versus-host disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response, Therapy

To determine the maximum tolerated dose of Venetoclax

Secondary objectives 5

1. To determine the safety of Venetoclax in aGVHD
2. To determine the remission rate of aGVHD and rate of progression to SR-aGVHD upon Venetoclax
3. To determine non-relapse mortality after Venetoclax in aGVHD
4. To determine overall survival after Venetoclax in aGVHD
5. To determine the effect of Venetoclax on aGVHD-causing effector cells in peripheral blood and affected tissue

Conditions and MedDRA coding

Acute graft-versus-host disease of the skin

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written informed consent, according to local guidelines, signed by the patients prior to any study related screening procedures are performed.
2. Male or female patients
3. ≥ 18 years old at the time of informed consent
4. Able to swallow tablets
5. Have undergone allo-HSCT from any donor source (matched unrelated, sibling, or haplo-identical donor) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non- myeloablative, myeloablative, and reduced intensity conditioning are eligible
6. Evident myeloid and platelet engraftment: Absolute neutrophil count (ANC) > 1000/mm AND Platelet count > 20,000 /mm3 (7)
7. Patients with newly clinically diagnosed aGVHD: aGVHD clinically diagnosed Grades II to IV as per standard criteria (13, 35, 36) occurring after allo HSCT requiring systemic immune suppressive therapy with prednisone 1-2 mg/kg bodyweight. Biopsy of involved organs with aGVHD is encouraged but not required for study screening. Evident myeloid and platelet engraftment (confirmed within 48h prior to study treatment start).

Exclusion criteria 6

1. Persons incapable of giving consent (permanently or temporarily)
2. Patients with relapsed primary malignancy, or who have been treated for relapse after allo HSCT
3. Known human immunodeficiency virus (HIV) infection
4. Active tuberculosis infection that developed after allo HSCT
5. Evidence of active viral disease including CMV, EBV, HHV -6, HBV, HCV, or BK virus.
6. Prior treatment with venetoclax

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Definition of the Maximum Tolerated Dose (MTD) after 28 and 56 days (Phase 1)

Secondary endpoints 10

1. Safety of Venetoclax in aGVHD after 28 and 56 days
2. Remission rate of aGVHD and rate of progression to SR-aGVHD upon Venetoclax
3. Non-relapse mortality and overall survival after Venetoclax in aGVHD
4. Effects of Venetoclax on aGVHD-causing effector cells in peripheral blood and affected tissue
5. Hematologic grade IV toxicities and Grade III/IV non-hematologic toxicities graded according to the NCI CTCAE criteria CTCAE version 4.03.
6. Efficacy of venetoclax
7. Inhibition of BCL2 pathway by venetoclax in peripheral blood and the skin on a single cell level
8. Immunological signature(s) by genome, epigenome and transcriptome sequencing
9. Baseline BCL2 activity identifying patients as responders or enabling monitoring of response to venetoclax by flow cytometry and immunofluorescence
10. Quality of life questionnaire, fatigue scale

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Dermatology

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Dermatology

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 11 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