Open label phase II study evaluating the efficacy and safety of the combination of tagraxofusp and venetoclax in treatment-naive blastic plasmacytoid dendritic cell neoplasm patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

French Innovative Leukemia Organization

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Dec 2025 → ongoing

Decision date (initial)

2025-05-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Abbvie · Stemline

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is the efficacy of the tagraxofusp + venetoclax combination (TAGVEN) as measured by the rate of composite complete remission (cCR), defined as complete remission (CR) or complete remission with incomplete marrow recovery (Cri), according to the European Leukemia Net 2022 definitions for AML and adapted for BPDCN) or complete response with minimal residual skin abnormality (CRc[clinical]) defined by a marked clearance of ≥ 75% of a patient’s skin lesions from baseline and a complete metabolic response after 3 cycles of the combination of tagraxofusp and venetoclax in adult patients with a treatment-naive BPDCN.

Secondary objectives 1

1. - Objective response rate (ORR) defined as cCR + partial response (PR) - Safety profile of the tagraxofusp and venetoclax combination - Incidence of Minimal Residual Disease (MRD) - Negative Responses measured by flow cytometry with a sensitivity of 0.1% - Progression-free Survival (PFS) - Relapse-free survival (RFS) - Duration of response (DOR) - Overall Survival (OS) - Number of patients bridged to allogeneic transplantation - Possible predictors of response with respect to cytogenetics and molecular status

Conditions and MedDRA coding

BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASMS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1.Patients with a confirmed BPDCN diagnosis according to WHO 2022 revised criteria and have not received previous treatment ; 2.Age >18 years ; 3.Ability to understand the protocol and to sign an informed consent ; 4.Possibility of follow-up ; 5.ECOG < 3 ; 6.Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 45 mL/min by the Cockcroft-Gault formula ; 7. Adequate cardiac function defined by LVEF >/= 50% by MUGA or ECHO and no clinically significant abnormalities on a 12-lead ECG ; 8.Albumin level≥3,2g/dL ; 9.Adequate liver function ; 10.Men, and women of childbearing potential must be using a highly effective method of contraception ; 11.Negative urine/blood pregnancy test within 1 week prior to the initiation of treatment

Exclusion criteria 1

1. 1. Participation to another clinical trial with any investigative drug within 30 days prior to study enrolment ; 2.Previous treatment with venetoclax or tagraxofusp ; 3.Concomitant immunosuppressive therapy –except for low-dose prednisone (≤10 mg/day) ; 4.Concomitant treatment with medications prohibited in association with venetoclax ; 5.Known allergy or sensitivity to tagraxofusp, venetoclax, and any of its components or excipients ; 6.Pregnant or breastfeeding woman ; 7.Peripheral neuropathy grade > 2 ; 8. Known positivity for hepatitis B or C infection except for those subjects with an undetectable viral load or subjects with serologic evidence of prior vaccination to HBV ; 9.Known HIV-positivity ; 10.Evidence of uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal) ; 11.Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study ; 12.Subject with a history of other malignancies prior to study ; 13.Malabsorption syndrome or other conditions that preclude enteral route of administration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who achieve a cCR after 3 TAGVEN cycles.

Secondary endpoints 1

1. - Objective response rate including cCR and partial remission after 3 TAGVEN cycles - Safety profile of the tagraxofusp and venetoclax combination - Proportion of patients with MRD - Negative responses measured by flow cytometry - Progression-free Survival - Duration of response - Overall Survival - Proportion of patients bridged to allogeneic stem cell transplantation - Possible predictors of response with respect to cytogenetics and mutational status

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

French Innovative Leukemia Organization

Sponsor organisation

French Innovative Leukemia Organization

Address

2 Boulevard Tonnelle

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

French Innovative Leukemia Organization

Contact name

Dr David Ghez

Public contact point

Organisation

French Innovative Leukemia Organization

Contact name

Dr David Ghez

Third parties 7

Locations

1 EU/EEA country · 34 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