Venetoclax SL-401 and Chemotherapy for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

  • STATUS
    Recruiting
  • End date
    Dec 31, 2026
  • participants needed
    40
  • sponsor
    M.D. Anderson Cancer Center
Updated on 9 December 2021

Summary

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.

Description

PRIMARY OBJECTIVE:

I. To evaluate progression-free survival (PFS) at 12 months of venetoclax (VEN) in combination with chemotherapy and SL-401 (tagraxofusp [TAG]) in patients with newly diagnosed blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SECONDARY OBJECTIVES:

I. To determine the safety of the SL-401 in combination with VEN and in combination with chemotherapy in patients with newly diagnosed BPDCN by toxicity and futility monitoring.

II. To determine the efficacy by measurement of progression free survival (PFS), overall response rate (ORR): complete response (CR) and complete response with incomplete marrow recovery (CRi), clinical complete response (CRc) and remission duration of SL-401 in combination with chemotherapy and VEN in patients with newly diagnosed BPDCN.

III. To determine the rate of stem cell translant (SCT) within the first 8 cycles (understanding that some patients won't get SCT) in patients with newly diagnosed BPDCN.

EXPLORATORY OBJECTIVES:

I. To examine expression and function of BCL-2 family proteins and its modulation by VEN in BPDCN blasts.

II. To determine the rate of minimal residual disease (MRD) negativity in patients achieving CR/CRi/CRc and its correlation with disease-free survival (DFS) and overall survival (OS).

III. To determine CD123 levels pre- and post-therapy. IV. To determine molecular mutations pre-and post- therapy as part of 81-gene panel by next-generation sequencing.

OUTLINE
INDUCTION

CYCLE 1: Patients receive tagraxofusp-erzs (SL-401) intravenously (IV) once daily (QD) over 15 minutes on days 1-5.

CYCLES 2, 4, 6, and 8: Patients receive tagraxofusp-erzs IV QD over 15 minutes on days 1-5, and venetoclax orally (PO) QD on days 1-14 of cycle 2, and days 1-7 of cycles 4, 6, and 8.

CYCLES 3 and 7: Patients receive venetoclax PO QD on days 1-7. Patients whose age < 60 receive hyper-CVAD and age >= 60 receive mini-hyper-CVD. Patients may receive rituximab IV over 90 minutes on days 1 and 8, methotrexate intrathecally (IT) on day 2, and/or cytarabine IT on day 8. Patients also receive venetoclax PO QD on days 1-7.

HYPER-CVAD (AGE < 60): Patients receive cyclophosphamide IV over 3 hours every 12 hours (Q12H) on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone orally (PO) or IV over 30 minutes on days 1-4 and 11-14, and doxorubicin IV over 24 hours on day 4.

MINI-HYPER-CVD (AGE >= 60): Patients receive cyclophosphamide IV over 3 hour Q12H on days 1-3, vincristine IV over 15 minutes on days 1 and 8, dexamethasone PO or IV over 30 minutes on days 1-4 and 11-14.

CYCLE 5: Patients receive venetoclax PO QD on days 1-7. Patients who age < 60 receive MTX/AraC and age >= 60 receive mini-MTX/AraC. Patients may receive rituximab IV over 4-6 hours on days 1 and 8, cytarabine IT on day 5, and/or methotrexate IT on day 8.

MTX/ARAC (AGE < 60): Patients receive methotrexate IV over 24 hours on day 1, and cytarabine IV over 3 hours Q12H on days 2 and 3.

MINI-MTX/ARAC (AGE >= 60): Patients receive methotrexate IV over 24 hours on day 1, methylprednisolone IV over 2 hours Q12H on days 1-3, and cytarabine IV over 3 hours Q12H on days 2 and 3.

ALL CYCLES: Treatment repeats every 28 days for 8 cycles in the absence of disease progression and unacceptable toxicity.

MAINTENANCE: Patients receive venetoclax PO QD on days 1-7, POMP chemotherapy during cycles 1-5, 7-11, and 13-17, and SL-401 IV QD on days 1-5 of cycles 6, 12, and 18. Treatment repeats every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity.

POMP: Patients receive mercaptopurine PO three time daily (TID) on days 1-28, vincristine IV over 15 minutes on day 1, prednisone PO QD on days 1-5, and methotrexate PO once weekly.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months thereafter.

Details
Condition Blastic Plasmacytoid Dendritic Cell Neoplasm
Treatment Rituximab, cyclophosphamide, methotrexate, cytarabine, prednisone, Methylprednisolone, Dexamethasone, vincristine, doxorubicin, Mercaptopurine, venetoclax, Tagraxofusp-erzs
Clinical Study IdentifierNCT04216524
SponsorM.D. Anderson Cancer Center
Last Modified on9 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically confirmed diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) per 2016 World Health Organization (WHO) criteria
Patients may have received emergent chemotherapy prior to study enrollment
One prior cycle of SL-401, or other BPDCN-directed therapy, will be allowed prior to entering the study
Prior or concomitant doses of aspacytarabine (ARA-C [cytarabine]) or hydroxyurea are allowed on before or during the study for proliferative disease due to BPDCN
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Albumin >= 3.2 g/dL (in the absence of receipt of intravenous albumin in the previous 72 hours)
Serum creatinine < 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
Total bilirubin < 1.5 x ULN (if total bilirubin is > 1.5 x but < 3 x 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 principal investigator [PI])
Ability to understand and the willingness to sign a written informed consent document
Able to adhere to study visit schedule and other protocol requirements including follow-up for survival assessment
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
Left ventricular ejection fraction >= institutional lower limit of normal by multi-gated acquisition (MUGA) scan or echocardiogram within 30 days of first protocol treatment

Exclusion Criteria

Patient is pregnant or breastfeeding
Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
Major surgery or radiation therapy within 14 days prior to the first study dose
Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the exception of hydroxyurea and/or dexamethasone, or one dose of cytarabine) prior to starting therapy
Symptomatic or untreated leptomeningeal disease or spinal cord compression
Patients 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)
Prior treatment with VEN
Malabsorption syndrome or other conditions that preclude enteral route of administration
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 patient inappropriate for enrollment into this study
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