CELL INTELLIGENCE · 肿瘤细胞治疗研究

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

主要终点：Progression free survival (PFS) · The median PFS time will be estimated by Bayesian posterior estimates. Estimated using the Kaplan-Meier method. · Up to 6 years；Incidence of adverse events · Will be reported by type, frequency and severity. Highest toxicity grades per patient per course will be tabulated for selected adverse events and laboratory measurements. · Up to 6 years；Overall response rate · Overall response rate along with complete remission and complete remission with incomplete hematologic recovery will be estimated along with 95% confidence interval. · Up to 6 years；Rate of stem cell transplant · The response rate will be compared between subgroups (e.g. minimal residual disease negativity, etc.) by Fisher's exact test, and Wilcoxon rank test will be used to compare the patient clinical information (e.g., protein expression) between subgroups such as response and non-response. · Up to 6 years

• Treatment (SL-401, venetoclax, chemotherapy) · EXPERIMENTAL · See detailed description.

This phase II trial studies how well venetoclax, SL-401, and chemotherapy works in treating patients with blastic plasmacytoid dendritic cell neoplasm. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. SL-401 is a recombinant protein consisting of IL-3 linked to a toxic agent called DT. IL-3 attaches to IL-3 receptors on tumor cells in a targeted way and delivers DT to kill them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and SL-401 with chemotherapy may be an effective treatment for patients with blastic plasmacytoid dendritic cell neoplasm.