Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm using Venetoclax and SL-401

Phase 2 Clinical Trial for Comprehensive Treatment Program for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Tagraxofusp (SL-401) in Combination With HCVAD/Mini-CVD and VENETOCLAX

This study is testing a combination of venetoclax, SL-401, and chemotherapy to see if it can help people with newly diagnosed blastic plasmacytoid dendritic cell neoplasm live longer and feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (other)
• Drugs / interventions: chemotherapy, radiation, rituximab, methotrexate, cyclophosphamide, doxorubicin, prednisone
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT04216524 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of venetoclax, SL-401, and chemotherapy in treating patients with newly diagnosed blastic plasmacytoid dendritic cell neoplasm (BPDCN). Venetoclax works by inhibiting enzymes necessary for tumor cell growth, while SL-401 targets IL-3 receptors on tumor cells to deliver a toxic agent that kills them. The study aims to assess progression-free survival at 12 months, safety, and overall response rates among participants. Additionally, it explores the molecular characteristics of the disease and the potential for stem cell transplantation.

Who should consider this trial

Good fit: Ideal candidates include treatment-naïve or relapsed/refractory adults aged 18 and older with a confirmed diagnosis of BPDCN.

Not a fit: Patients with other types of cancer or those who have received extensive prior treatment for BPDCN may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with blastic plasmacytoid dendritic cell neoplasm.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Treatment naïve or relapsed refractory patients with histologically confirmed diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) per 2016 WHO criteria
2. Front line participants may have received emergent chemotherapy prior to study enrollment:

   1. One prior cycle of SL-401, or other BPDCN-directed therapy, will be allowed prior to entering the study.
   2. Prior or concomitant doses of ARA-C (cytarabine) or Hydroxyurea are allowed on before or during the study for proliferative disease due to BPDCN.
3. Relapsed/refractory participants may have received at least one prior cycle of therapy.
4. Age ≥ 18 years
5. ECOG performance status 0, 1, or 2 (see APPENDIX B)
6. Adequate organ function as defined by:

   * Albumin ≥ 3.2 g/dL (in the absence of receipt of intravenous albumin in the previous 72 hours)
   * Serum creatinine \< 1.5x ULN
   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5x ULN
   * Total bilirubin \< 1.5x ULN (if total bilirubin is \> 1.5x but \< 3x ULN, and thought to be elevated due to Gilbert's disease or the patient's BPDCN, the subject may be eligible but must discuss with the PI)
7. Ability to understand and the willingness to sign a written informed consent document.
8. Able to adhere to study visit schedule and other protocol requirements including follow-up for survival assessment
9. Women of child-bearing potential and men enrolled on this protocol must agree to use adequate contraception for the duration of study participation and for 2 months after completion VEN administration. Acceptable birth control methods allowed to be used while on study include:

   * Birth control pills or injections
   * Intrauterine devices (IUDs)
   * Double-barrier methods for example condom in combination with spermicide. Males should not donate sperm while on study and for at least 8 weeks after the last dose of SL-401.
10. Left ventricular ejection fraction ≥ institutional lower limit of normal by MUGA scan or echocardiogram within 30 days of first protocol treatment.

Exclusion Criteria:

1. Participants is pregnant or breastfeeding
2. Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
3. Major surgery or radiation therapy within 14 days prior to the first study dose
4. Symptomatic or untreated leptomeningeal disease or spinal cord compression
5. Participants with active heart disease (New York Heart Association (NYHA) class 3-4 as assessed by history and physical examination, unstable angina/stroke/myocardial infarction within the last 6 months)
6. Malabsorption syndrome or other conditions that preclude enteral route of administration
7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the participants inappropriate for enrollment into this study

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Principal investigator: Naveen Pemmaraju — M.D. Anderson Cancer Center
• Study coordinator: Naveen Pemmaraju

Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm