Clinical trial NCT07007052: Phase II Study Evaluating the Efficacy and Safety of the Combination of Tagraxofusp and Venetoclax in Treatment-naive Blastic Plasmacytoid Dendritic Cell Neoplasm Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Stemline Therapeutics, Inc.
name: AbbVie
First posted: 2025-06-05
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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
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 ≥ 60 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 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
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 (if applicable)
12. Patient covered by any social security system

Exclusion Criteria:

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. Treatment of BPDCN with any prior chemotherapy or investigational agents, except hydroxyurea for less than 14 days at the time of inclusion
4. Concomitant immunosuppressive therapy -except for low-dose prednisone (≤10 mg/day)
5. Known allergy or sensitivity to tagraxofusp, venetoclax, and any of its components or excipients.
6. Pregnant or breastfeeding woman
7. 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
8. Evidence of uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal)
9. 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.
10. 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.
11. Malabsorption syndrome or other conditions that preclude enteral route of administration
12. Patient with hereditary fructose intolerance

Primary outcomes:
measure: Proportion of participants who achieve a cCR (CR or Cri or CRc) after 3 TAGVEN cycles
timeFrame: From enrollment to the end of the third 28 days-cycle
Secondary outcomes:
Other outcomes:
Locations:
city: Amiens
country: France
facility: AMIENS - CH Amiens Picardie Site Sud
city: Angers
country: France
facility: ANGERS - CHU - Maladies du sang
city: Argenteuil
country: France
facility: ARGENTEUIL - Centre hospitalier Victor Dupouy
city: Avignon
country: France
facility: AVIGNON - Centre Hospitalier
city: Besançon
country: France
facility: BESANCON - Hôpital Jean Minjoz - Hématologie
city: Clamart
country: France
facility: CLAMART - Hôpital d'Instruction des Armées de Percy
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand - Chu Estaing
city: Corbeil-Essonnes
country: France
facility: Corbeil-Essonnes - Ch Sud Francilien
city: Créteil
country: France
facility: AP-HP- CRETEIL - CHU Henri Mondor
city: Grenoble
country: France
facility: Grenoble CHU - Hématologie Clinique
city: Lille
country: France
facility: LILLE CHU - Hôpital Claude Huriez
city: Limoges
country: France
facility: Limoges CHU
city: Lyon
country: France
facility: LYON HCL- Site Sud
city: Marseille
country: France
facility: MARSEILLE - Institut Paoli-Calmettes
city: Metz
country: France
facility: METZ - CHR Metz-Thionville
city: Montpellier
country: France
facility: Montpellier - Chu Saint Eloi
city: Mulhouse
country: France
facility: MULHOUSE GHRMSA - Hôpital E. Muller - Hématologie
city: Nantes
country: France
facility: NANTES - Hôpital Hôtel Dieu - Hématologie Clinique
city: Nîmes
country: France
facility: Nimes CHU
city: Paris
country: France
facility: APHP - Hôpital Saint-Louis - Hématologie adultes
city: Paris
country: France
facility: APHP - HOPITAL COCHIN - Hématologie
city: Paris
country: France
facility: AP-HP - Hôpital Necker
city: Pessac
country: France
facility: BORDEAUX - Hôpital Haut-Levêque
city: Poitiers
country: France
facility: POITIERS - Hôpital La Milétrie - Hématologie Clinique
city: Reims
country: France
facility: REIMS - Hôpital Robert Debré - Hématologie Clinique
city: Rennes
country: France
facility: RENNES - CHU Pontchaillou - Hématologie Clinique
city: Rouen
country: France
facility: ROUEN - Centre Henri Becquerel - Service Hématologie Clinique
city: Saint-Etienne
country: France
facility: CHU SAINT-ETIENNE - iCHUSE
city: Strasbourg
country: France
facility: Strasbourg - Institut de Cancerologie Strasbourg
city: Toulouse
country: France
facility: Toulouse - IUCT Oncopole - Service d'Hématologie
city: Tours
country: France
facility: TOURS - Hôpital Bretonneau
city: Vandœuvre-lès-Nancy
country: France
facility: NANCY - CHU de Brabois
city: Versailles
country: France
facility: VERSAILLES - Hôpital André Mignot
city: Villejuif
country: France
facility: Villejuif Igr - Gustave Roussy
Study officials:
References: