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

Overview

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.

Interventions

• Drug Venetoclax
  Single interventional arm
• Drug Tagraxofusp
  Single interventional arm

Primary outcome measures

• Proportion of participants who achieve a cCR (CR or Cri or CRc) after 3 TAGVEN cycles [Time frame: From enrollment to the end of the third 28 days-cycle]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• Participation to another clinical trial with any investigative drug within 30 days prior to study enrolment.
• Previous treatment with venetoclax or tagraxofusp
• Treatment of BPDCN with any prior chemotherapy or investigational agents, except hydroxyurea for less than 14 days at the time of inclusion
• 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.
• Malabsorption syndrome or other conditions that preclude enteral route of administration
• Patient with hereditary fructose intolerance

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 34 centers

• AMIENS - CH Amiens Picardie Site Sud — Amiens
• ANGERS - CHU - Maladies du sang — Angers
• ARGENTEUIL - Centre hospitalier Victor Dupouy — Argenteuil
• AVIGNON - Centre Hospitalier — Avignon
• BESANCON - Hôpital Jean Minjoz - Hématologie — Besançon
• CLAMART - Hôpital d'Instruction des Armées de Percy — Clamart
• Clermont-Ferrand - Chu Estaing — Clermont-Ferrand
• Corbeil-Essonnes - Ch Sud Francilien — Corbeil-Essonnes
• … and 26 more centers

Identifiers

NCT: NCT07007052 · TAGVEN

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗