Clinical Trial: NCT04216524 - My Cancer Genome

NCT04216524

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.

Related Conditions:

Blastic Plasmacytoid Dendritic Cell Neoplasm

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04216524

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: 2019-0587
SECONDARY ID: NCI-2019-08358
SECONDARY ID: 2019-0587
SECONDARY ID: P30CA016672
NCT ID: NCT04216524

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

Drug	Synonyms	Arms
Cyclophosphamide	(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Treatment (SL-401, venetoclax, chemotherapy)
Cytarabine	.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453	Treatment (SL-401, venetoclax, chemotherapy)
Dexamethasone	Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex	Treatment (SL-401, venetoclax, chemotherapy)
Doxorubicin	Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin	Treatment (SL-401, venetoclax, chemotherapy)
Mercaptopurine	3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, Bw 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785	Treatment (SL-401, venetoclax, chemotherapy)
Methotrexate	Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039	Treatment (SL-401, venetoclax, chemotherapy)
Methylprednisolone	Adlone, Caberdelta M, DepMedalone, Depo Moderin, Depo-Nisolone, Duralone, Emmetipi, Esametone, Firmacort, Medlone 21, Medrate, Medrol, Medrol Veriderm, Medrone, Mega-Star, Meprolone, Methylprednisolonum, Metilbetasone Solubile, Metrocort, Metypresol, Metysolon, Predni-M-Tablinen, Prednilen, Radilem, Sieropresol, Solpredone, Summicort, Urbason, Veriderm Medrol, Wyacort	Treatment (SL-401, venetoclax, chemotherapy)
Prednisone	.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone	Treatment (SL-401, venetoclax, chemotherapy)
Rituximab	ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima	Treatment (SL-401, venetoclax, chemotherapy)
Tagraxofusp-erzs	Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris, IL3R-targeting Fusion Protein SL-401, SL-401, Tagraxofusp, Tagraxofusp ERZS	Treatment (SL-401, venetoclax, chemotherapy)
Venetoclax	ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto	Treatment (SL-401, venetoclax, chemotherapy)
Vincristine	Leurocristine, VCR, Vincrystine	Treatment (SL-401, venetoclax, chemotherapy)

Purpose

Detailed 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.

Trial Arms

Name	Type	Description	Interventions
Treatment (SL-401, venetoclax, chemotherapy)	Experimental	See detailed description.	Cyclophosphamide Cytarabine Dexamethasone Doxorubicin Mercaptopurine Methotrexate Methylprednisolone Prednisone Rituximab Tagraxofusp-erzs Venetoclax Vincristine

Eligibility Criteria

        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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Progression free survival (PFS)
Time Frame:	Up to 6 years
Safety Issue:
Description:	The median PFS time will be estimated by Bayesian posterior estimates. Estimated using the Kaplan-Meier method.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

January 14, 2021

Clinical Trials /

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