Phase II Study Evaluating the Efficacy and Safety of the Combination of Tagraxofusp and Venetoclax in Treatment-naive Blastic Plasmacytoid Dendritic Cell Neoplasm Patients

NCT07007052 | Not Yet Recruiting Phase 2

• 1 other identifier: TAGVEN
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 34

Brief Summary

The goal of this clinical trial is to study the efficacy of the tagraxofusp + venetoclax combination in treatment-naive blastic plasmacytoid dendritic cell neoplasm adult patients. The main question is to verify the response in patients after 3 cycles of tagraxofusp+venetolax and to demonstrate if the combination of tagraxofusp + venetoclax increases the rate of complete remission, assessed after 3 months of treatment. Patients will receive a ramp-up phase of venetoclax during 3 days and at least 3 cycles of venetoclax. After, the investigators will evaluate the response, and depending on the response observed, patients may receive additional cycles of treatment for a maximum of 24 cycles, or receive an allograft or discontinue the treatment in the case of therapeutic failure.

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Keywords

blastic plasmacytoid dendritic cell neoplasm; Combination of venetoclax + tagraxofusp; Composite complete remission; Complete remission; Evaluation of response

Outcome Measures

Primary Outcomes (1)

• Proportion of participants who achieve a cCR (CR or Cri or CRc) after 3 TAGVEN cycles

  Evaluation will be done with a bone marrow aspirate, cytogenetics, metabolic imaging, study of MRD by NGS and flow-cytometry and SWAT SCORE

  From enrollment to the end of the third 28 days-cycle

Study Arms (1)

Single interventional arm

EXPERIMENTAL

For each 28 days-cycle of treatment : * venetoclax 400mg/day orally after a ramp-up period of 3-days * tagraxofusp starting at the end of the venetoclax ramp-up period i.e. at day 4 for twelve 28-days cycles, 12 μg/kg body weight administered as an intravenous infusion over 15 minutes, once daily, on days 1-3 of each cycle

Drug: Venetoclax; Drug: Tagraxofusp

Interventions

Venetoclax DRUG

Single interventional arm

Also known as: ABT-199, GDC-0199, RG7601, selective BCL-2 inhibitor

Single interventional arm

Tagraxofusp DRUG

Single interventional arm

Also known as: SL-401, CD123-directed cytotoxin

Single interventional arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a confirmed BPDCN diagnosis according to WHO 2022 revised criteria and have not received previous treatment : patients with skin or lymph node lesions but no bone marrow involvement can be included
• Age \>18 years
• Ability to understand the protocol and to sign an informed consent
• Possibility of follow-up
• ECOG \< 3
• Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 60 mL/min by the Cockcroft-Gault formula.
• Adequate cardiac function defined by LVEF \>/= 50% by MUGA or ECHO and no clinically significant abnormalities on a 12-lead ECG
• Albumin level≥3,2g/dL
• Adequate liver function as demonstrated by:
• aspartate aminotransferase (AST) ≤ 2.5 × ULN\*
• alanine aminotransferase (ALT) ≤ 2.5 × ULN\*
• bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome\* \* Unless considered due to leukemic organ involvement, in that cases values must be ≤ 10 × ULN
• Men, and women of childbearing potential must be using a highly effective method of contraception
• Negative urine/blood pregnancy test within 1 week prior to the initiation of treatment (if applicable)
• Patient covered by any social security system

You may not qualify if:

• Participation to another clinical trial with any investigative drug within 30 days prior to study enrolment.
• Previous treatment with venetoclax or tagraxofusp
• Concomitant immunosuppressive therapy -except for low-dose prednisone (≤10 mg/day)
• Known allergy or sensitivity to tagraxofusp, venetoclax, and any of its components or excipients.
• Pregnant or breastfeeding woman
• 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
• Evidence of uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal)
• 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 including, but not limited to:
• Cardiovascular disease e.g., NYHA heart failure \> class 2, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension, or clinically significant arrythmias not controlled by medication.
• Renal, pulmonary, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
• Subject with a history of other malignancies within the last three years prior to study entry, except for:
• Adequately treated in situ carcinoma of the breast or cervix uteri
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
• Prostate cancer without needs for specific therapy
• Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Stemline Therapeutics, Inc.: collaborator
• AbbVie: collaborator

Study Sites (34)

AMIENS - CH Amiens Picardie Site Sud

Amiens, 80054, France

Location

ANGERS - CHU - Maladies du sang

Angers, 49933, France

Location

ARGENTEUIL - Centre hospitalier Victor Dupouy

Argenteuil, France

Location

AVIGNON - Centre Hospitalier

Avignon, 84000, France

Location

BESANCON - Hôpital Jean Minjoz - Hématologie

Besançon, 25030, France

Location

CLAMART - Hôpital d'Instruction des Armées de Percy

Clamart, 92140, France

Location

Clermont-Ferrand - Chu Estaing

Clermont-Ferrand, 63000, France

Location

Corbeil-Essonnes - Ch Sud Francilien

Corbeil-Essonnes, France

Location

AP-HP- CRETEIL - CHU Henri Mondor

Créteil, 94000, France

Location

Grenoble CHU - Hématologie Clinique

Grenoble, 38043, France

Location

LILLE CHU - Hôpital Claude Huriez

Lille, 59037, France

Location

Limoges CHU

Limoges, France

Location

LYON HCL- Site Sud

Lyon, France

Location

MARSEILLE - Institut Paoli-Calmettes

Marseille, 13000, France

Location

METZ - CHR Metz-Thionville

Metz, 57085, France

Location

Montpellier - Chu Saint Eloi

Montpellier, France

Location

MULHOUSE GHRMSA - Hôpital E. Muller - Hématologie

Mulhouse, 68070, France

Location

NANTES - Hôpital Hôtel Dieu - Hématologie Clinique

Nantes, 44093, France

Location

Nimes CHU

Nîmes, France

Location

APHP - Hôpital Saint-Louis - Hématologie adultes

Paris, 75010, France

Location

APHP - HOPITAL COCHIN - Hématologie

Paris, 75014, France

Location

AP-HP - Hôpital Necker

Paris, 75015, France

Location

BORDEAUX - Hôpital Haut-Levêque

Pessac, 33600, France

Location

POITIERS - Hôpital La Milétrie - Hématologie Clinique

Poitiers, 86000, France

Location

REIMS - Hôpital Robert Debré - Hématologie Clinique

Reims, 51100, France

Location

RENNES - CHU Pontchaillou - Hématologie Clinique

Rennes, 35033, France

Location

ROUEN - Centre Henri Becquerel - Service Hématologie Clinique

Rouen, 76038, France

Location

CHU SAINT-ETIENNE - iCHUSE

Saint-Etienne, 42271, France

Location

Strasbourg - Institut de Cancerologie Strasbourg

Strasbourg, 67200, France

Location

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, France

Location

TOURS - Hôpital Bretonneau

Tours, 37000, France

Location

NANCY - CHU de Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

VERSAILLES - Hôpital André Mignot

Versailles, France

Location

Villejuif Igr - Gustave Roussy

Villejuif, 94804, France

Location

MeSH Terms

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm; Pathologic Complete Response

Interventions

venetoclax; tagraxofusp

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Leukemia; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 5, 2025
• Study Start: December 1, 2025
• Primary Completion: January 31, 2026
• Study Completion (Estimated): September 30, 2031
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (34)