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

Blastic Plasmacytoid Dendritic Cell Neoplasm Clinical Trial

Official title: 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

Status Recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Neoplasms

• NCT number: NCT04216524
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Naveen Pemmaraju
• Phone: 713-792-4956
• Email: npemmaraju@mdanderson.org
• Status: Recruiting
• Phase: Phase 2
• Start date: May 29, 2020
• Completion date: December 31, 2026