Tagraxofusp (SL-401) Therapy for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Patients Post-Autologous or Post-Allogeneic Hematopoietic Cell Transplantation
Phase: PHASE2
Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm
Sponsor: M.D. Anderson Cancer Center

 
 
 
 
 
 
 
Tagraxofusp (SL-401) therapy for blastic plasmacytoid dendritic cell 
neoplasm (BPDCN) patients post-autologous or post-allogeneic 
hematopoietic cell transplantation 
 
 
 
 
 
 
 
Institution Study Number: 
2018-0646 
Financial Support: 
Stemline Therapeutics, Inc. 
IND Holder: 
The University of Texas MD Anderson Cancer Center 
IND Number: 
144754 
Principal Investigator: 
Qaiser Bashir, MD 
The University of Texas MD Anderson Cancer Center 
Stem Cell Transplantation and Cellular Therapy Department 
1515 Holcombe Blvd, Unit 0423 
Houston, TX 77030 
Telephone: 713.794.4422 
Fax: 713.792.8949 
qbashir@mdanderson.org 
Co-Chairs: 
Naveen Pemmaraju, MD 2 
Muzaffar H. Qazilbash, MD1 
Collaborator: 
  Denái R. Milton, MS3 
 
  
 
 
1 The University of Texas MD Anderson Cancer Center, Stem Cell Transplantation and Cellular Therapy Department 
2 The University of Texas MD Anderson Cancer Center, Leukemia Department 
3 The University of Texas MD Anderson Cancer Center, Biostatistics Department 

Table of Contents 
 
1.0 Objectives ............................................................................................................................................................................ 3 
Primary Objective ............................................................................................................................................................................................................................... 3 
Secondary Objectives .......................................................................................................................................................................................................................... 3 
2.0 Background and Rationale ................................................................................................................................................... 3 
2.1 
Treatment of BPDCN ................................................................................................................................................................................................................. 4 
2.2.2 Other Empirical Approaches for the Treatment of BPDCN ........................................................................................................................................................ 5 
2.2.3 Autologous HCT ......................................................................................................................................................................................................................... 7 
2.2.4 Allogeneic HCT .......................................................................................................................................................................................................................... 7 
2.3 
Rationale for tagraxofusp use in this study ............................................................................................................................................................................... 8 
2.3.1 Background drug information (Tagraxofusp) ............................................................................................................................................................................ 8 
2.3.2 Safety data ................................................................................................................................................................................................................................ 9 
2.3.3 Carcinogenesis, Mutagenesis, and Impairment of Fertility ..................................................................................................................................................... 12 
3.0 Patient Eligibility ................................................................................................................................................................ 12 
3.1 
Inclusion criteria ...................................................................................................................................................................................................................... 12 
3.2 
Exclusion criteria ..................................................................................................................................................................................................................... 13 
4.0 Treatment Plan .................................................................................................................................................................. 14 
4.1 
Treatment initiation ................................................................................................................................................................................................................ 14 
4.2 
Treatment duration ................................................................................................................................................................................................................. 14 
4.3 
Pre-medication........................................................................................................................................................................................................................ 14 
4.4 
Dose and schedule .................................................................................................................................................................................................................. 14 
4.5 
Route and Administration ....................................................................................................................................................................................................... 15 
4.6 
Dose modifications for tagraxofusp related hematological toxicity ........................................................................................................................................ 15 
4.7 
Discontinuation of treatment.................................................................................................................................................................................................. 16 
4.8 
Procedures During Dosing Period ........................................................................................................................................................................................... 16 
4.8 
Management of Specific Toxicities Capillary leak syndrome (CLS) .......................................................................................................................................... 17 
5.0 Evaluation During Study ..................................................................................................................................................... 17 
5.1 
Disease specific monitoring ..................................................................................................................................................................................................... 18 
5.2 
Evaluations during follow up ................................................................................................................................................................................................... 19 
5.3 
Duration of follow up .............................................................................................................................................................................................................. 19 
5.4 
Outside Physician Participation During Treatment ................................................................................................................................................................. 19 
6.0 Adverse Events and Reporting Requirements ..................................................................................................................... 20 
6.1 
Serious Adverse Event (SAE) Reporting ................................................................................................................................................................................... 21 
7.0 Criteria for Removal from the Study ................................................................................................................................... 24 
8.0 Statistical Considerations ................................................................................................................................................... 24 
Table 4 Stopping criteria ................................................................................................................................................................................................................... 25 
9.0 References ......................................................................................................................................................................... 27 
 

 
 
         
             
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Protocol Body 
 
1.0 Objectives 
 
Primary Objective 
 
To evaluate the safety of tagraxofusp in patients with blastic plasmacytoid dendritic cell 
neoplasm (BPDCN) after autologous (auto) or allogeneic (allo) hematopoietic cell 
transplantation (HCT). 
 
Secondary Objectives 
1. To estimate progression-free survival (PFS) in patients with BPDCN receiving maintenance 
therapy with tagraxofusp after auto-HCT or allo-HCT. 
2. To estimate the overall survival (OS) in patients with BPDCN receiving maintenance therapy 
with tagraxofusp after auto-HCT or allo-HCT. 
2.0 Background and Rationale 
BPDCN is a rare hematologic malignancy. The exact incidence is unknown because of 
changing nomenclature over time and a variety of clinical presentations. Nevertheless, it is 
estimated that BPDCN accounts for approximately 0.44% of all hematologic malignancies and 
approximately 0.7% of cutaneous lymphomas as misdiagnosed cases. When coupled with 
accurately diagnosed cases, the incidence is estimated at about 500 new cases, or more, in the 
U.S. per year.1 Males are more commonly affected by BPDCN with a male/female ratio of 
3.5/1 and the median age at diagnosis is 66 years.2 
 
Pathogenesis: BPDCN arises from precursors of myeloid origin, the plasmacytoid dendritic 
cells (pDC; type 2 dendritic cells)3. There is no single genetic abnormality that has been 
identified as the hallmark of BPDCN, however, a wide array of chromosomal aberrations has 
been described including a complex karyotype with deletions on chromosomes 5q21 or 5q34 
(72%), 12p13 (64%), 13q13-q21 (64%), 6q23-qter (50%), 15q (43%) and 9 (28%) and sporadic 
genetic alterations affecting RB1, LATS2, CDKN1B, CDKN2A, and TP53 gene.3  In addition, 
TET24 and FLT3-ITD1 mutations have also been described in the literature. 
 
Clinical presentation: The clinical behavior of BPDCN is usually aggressive. Skin lesions are 
frequently the initial manifestation of the disease, prompting medical advice5, with the face or 
scalp commonly affected.6  Without further therapy, the disease can rapidly progress and 
result in cytopenias due to bone marrow involvement, lymphadenopathy, and splenomegaly.5 
Some patients present with disseminated disease at the outset, with multi-organ involvement. 
In a large analysis of patients with BPDCN with leukemic presentation, 23% did not have any 
skin lesions.1 The blasts can be frequently identified in the blood but hyperleukocytosis is not 
common.5 Other reported sites of involvement include central nervous system (CNS), eyes, 
paranasal cavities, tonsils, lungs, and soft tissues.5 The neuromeningeal involvement ranges 
between 4-9% at diagnosis and 17-33% at relapse.5 
 

 
 
         
             
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Immunophenotype: BPDCN tumor cells express CD4 and CD56 (WHO classification, 2017). 
In addition, the expression of at least one pDC-associated marker, BDCA-2 (blood dendritic cell 
antigen-2, also termed CD303, CLEC4E), CD123 (also termed interleukin-3 alpha-chain, 
IL3RA), TCL1 (also termed TCL1A)], or SPIB is needed5. Tumor cells lack marker expression 
for B cells, T cells, myeloid or monocytic cells, and NK cells5. CD5, CD7, CD33, and 
cytoplasmic CD3 may be positive in some cases.5 
 
Diagnosis: The diagnosis of BPDCN can be challenging due to lack of specific chromosomal 
abnormalities. Several immunophenotypic variations have been described
5. A large series of 
more than 300 published cases suggested that CD123, CD4, CD56, and TCL1 are the most 
reliable markers to establish the diagnosis of BPDCN.7 
 
Differential diagnosis: BPDCN needs to be differentiated from extranodal (nasal-type) CD56+ 
NK/T-cell lymphoma (often associated with EBV), cutaneous T-cell lymphoma (usually do not 
express CD56, CD123, and BDCA2), CD33+AML CD4+/CD56+, undifferentiated AML, AML 
with myelomonocytic/monocytic differentiation, or ambiguous lineage leukemia (most AML 
cases are usually positive for MPO and express myeloid antigens such as CD13, CD15, and 
CD117). 
2.1 Treatment of BPDCN 
2.1.1 Tagraxofusp 
 
Tagraxofusp (SL-401), a targeted therapy directed to CD123 (the a subunit of the IL3 receptor). 
Tagraxofusp is comprised of recombinant human interleukin-3 (IL-3) fused to a truncated 
diphtheria toxin payload. It is composed of IL3 fused via a Met-His linker to the catalytic and 
translocation domains of a truncated diphtheria toxin (DT).14-19 The IL3 domain of tagraxofusp 
binds to its natural receptor, IL3 receptor which is then internalized, leading to translocation of 
the DT A fragment to the cytosol, followed by ADP ribosylation of elongation factor 2, 
inactivation of protein synthesis, and cell death.14 Tagraxofusp inhibits protein synthesis and 
DT-GMCSF fusion proteins have been shown to active and subsequently kill leukemic cells in 
the resting G0 phase.20 BPDCN blasts overexpress CD123, and tagraxofusp demonstrated 
impressive preclinical and, subsequently, clinical results. 
 
Delettre et al. assessed the cytotoxicity of tagraxofusp in BPDCN patient-derived cell lines 
(CAL-1 and GEN2.2) and primary BPDCN cells isolated directly from patients (n = 12).21  Cells 
were treated for 18 or 48 hours with tagraxofusp single agent and were then compared cells 
treated with other cytotoxic agents. Cells rerated with tagraxofusp at concentrations 
substantially lower than peak concentrations achieved in patients, induced a 92% decrease in 
viability of BPDCN cell lines and 80% in primary BPDCN cells, more effective than most 
chemotherapeutic agents. Furthermore, NOD-SCID mice were treated with 2Gy radiation 
followed by injection of GEN 2.2 cells. Mice were then treated with tagraxofusp at clinically 
relevant doses. The median OS was significantly longer in mice receiving therapy with 
tagraxofusp vs. untreated controls (53 days vs. 15 days, respectively). 
 
The first clinical experience of tagraxofusp in patients with BPDCN was in a Phase 1/2 study, in 
which 11 patients with BPDCN received a single course of 12.5 mcg/kg IV over 15 minutes daily 
for up to 5 doses (Frankel et al).14 Seven of 9 evaluable first-line or relapsed/refractory BPDCN 
patients (78%) had major response (5 CR and 2 PR) with a single course of tagraxofusp. The 
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Reference 
Location, N 
Diagnostic 
criteria 
Treatment 
CR 
rate 
Response 
duration 
Proportion 
bridged to 
SCT 
Survival 
from 
diagnosis 
treatment x 2 
(37%) 
17/41 
(41%)d 
Poret 
- 
AML-like x 19 
34/80 
Median 
34/80 
Median = 8 
(2015) 
ALL-like x 17 
(43%) DOR 8-14 
(43%) 
months 
France 
CHOP-like x 16 
months 
N=86 
NK/T-like x 16 
across the 
Other x 12 
different 
treatments 
Feuillard 
CD4+/CD56+ 
Polychemothera 
18/23 
Median 
2/20 
Median = 
(2002) 
France 
N=23 
DC2 cells 
py 
N=2 untreated 
(78%) DOR = 9 
months 
(10%) 
adults 
12 months 
Petrella 
CD4+/CD56+ 
Polychemo 
21/28 
Median 
- 
Median for 
(2005) 
France/ 
(CD123 
PDCs) 
therapy 
N=2 untreated 
e 
(78%) 
DOR = 11 
months 
those 
treated 
= 
Netherlands 
13 months 
N=30 
 
a = Aggressively treated patients. 
b = All treated patients (including palliative cases). 
c = After induction therapy. 
d = After consolidation therapy. 
e = 21/28 patients showed a “good response”. The term “CR” was not used. 
 
2.2.3 
Autologous HCT 
 
The data regarding auto-HCT in BPDCN is limited to small case series. There is no consensus 
on optimal conditioning regimens. In a report, Reimer et al.16 treated 4 patients with 
Cyclophosphamide-Total body irradiation (TBI) +/- Etoposide. Three patients died, all from 
disease relapse. One patient was alive and in CR. In another series of 6 patients by Suzuki et 
al.17, median survival was 13.5 months with auto-HCT, however, the conditioning regimen was 
no specified. In a recent analysis by Kharfan-Dabaja et al.15, outcomes of 8 patients with 
BPDCN who underwent auto-HCT were reported. Five of the 8 patients were in CR at the time 
of auto-HCT. Median age was 67 (45-72) years. One-year PFS and OS were 11%. The median 
PFS and OS was 12 months for both endpoints. 
 
2.2.4 
Allogeneic HCT 
 
The outcomes of BPDCN are more favorable in patients receiving allo-HCT, with long-term 
remissions more likely in patients who receive SCT in CR. 
18 In an Italian study by Pagano et al., 
1 

 
 
         
             
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1
1
43 patients were retrospectively analyzed. In the 6 patients that received allo-HCT the OS was 
22.7 months (range 12-32.9) compared to the non-transplanted patients in whom the OS was 
7.1 months (p=0.03). In a registry report from the European Group for Blood and Marrow 
Transplantation (EBMT), 34 patients with BPDCN who received allo-HCT [myeloablative 
conditioning (MAC) in 74%; 56% in CR1) had a 3-year cumulative incidence of relapse, 
disease-free survival (DFS), and OS of 32%, 33%, and 41%, respectively. 
Three-year 
non-relapse mortality (NRM) was 30%. Patients who underwent allo-HCT in CR1 trended 
toward better 3-year DFS (36%) and OS (52%) compared with patients who underwent 
allo-HCT during more advanced disease (DFS, 26%; OS, 29%). All patients who received 
reduced intensity conditioning (RIC) experienced early relapse or early death and no patient 
achieved long-term disease control. In a more recent report, outcomes of 37 patients with 
BPDCN undergoing allo-HCT at different centers in the US were analyzed. 
The median age 
was 50 (range: 14-74) years. One-year and 3-year OS was 68% and 58%, respectively. 
Three-year OS in patients receiving allo-HCT in CR1 was 74% vs 0% in patients transplanted 
beyond CR1 (p < 0.0001). 
 
In summary, the available data suggest that long-term remission can be expected in 
approximately 50% of patients undergoing allo-HCT. The outcomes are significantly superior if 
patients are transplanted in CR1. However, the relapse rate remains a major concern and 
strategies are needed to minimize this risk. 
 
2.3 
Rationale for tagraxofusp use in this study 
As evident from the above data, BPDCN is an aggressive disease with limited therapeutic 
options. Patients undergoing allo-HCT can have long-term remissions, however, despite 
allo-HCT the relapse rate remains high. BPDCN blasts overexpress CD123 and tagraxofusp, 
which targets the IL-3 receptor has shown impressive clinical activity with unprecedented 
response rates. This study intends to assess the safety and clinical activity of tagraxofusp in 
patients with BPDCN post-HCT, in attempt to reduce the rate of post-HCT relapse and improve 
OS. 
 
2.3.1 
Background drug information (Tagraxofusp) 
 
Tagraxofusp is a 524- amino acid recombinant fusion protein expressed in Escherichia coli from 
a hybrid gene comprised of a DNA sequence of human IL-3 recombinantly fused to a truncated 
DT payload engineered such that IL-3 replaces the native DT receptor-binding domain. In this 
way, the IL-3 domain of tagraxofusp directs the cytotoxic truncated DT payload to cells that 
express CD123. After binding to the CD123, tagraxofusp is internalized by receptor-mediated 
endocytosis and localized to early endosomes. The translocation domain of DT changes 
conformation in the acidic environment of the endosome, and the RXRR motif (residues 
191-194) located between the catalytic and translocation domains of DT is cleaved by 
endosomal furin. The translocation domain of DT then inserts into the endosomal membrane. 
As the TAT-like domain of DT (residues 201-230) interacts with cytosolic heat shock protein 90 
(Hsp90) and thioreduxin reductase, the catalytic domain (A fragment) unfolds, is reduced, and 
translocates to the cytosol. Upon release into the cytosol, the A fragment refolds and 
catalytically inactivates cellular protein synthesis by adenosine diphosphate (ADP)-ribosylating 
the diphthamide residue in domain IV of elongation factor 2 (EF-2), leading to apoptosis 
(Investigator Brochure). 

 
 
         
             
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2.3.2 
Safety data 
The most common individual treatment emergent adverse events (TEAEs) reported to date with 
tagraxofusp, regardless of dose, were ALT increased (69 patients, 55%) and AST increased (68 
patients; 54%); hypoalbuminemia (66 patients; 53%); fatigue (61 patients, 49%); nausea (58 
patients; 46%); peripheral edema (55 patients; 44%); pyrexia (54 patients; 43%); 
thrombocytopenia (44 patients; 35%), and headache and hyperglycemia (each 38 patients; 
30%). A summary of the most common (i.e.; incidence ·10%) TEAEs reported among 
tagraxofusp -treated patients, regardless of dose, is presented in Table 2. See Version 4.0 of 
the SL-401 Investigators Brochure for additional safety information. 
 
Table 2. 
 Most Common (³ 10%) Treatment-Emergent Adverse Events, Overall and by 
Indication/Study, by MedDRA Preferred Term (Safety Population) 
 
Stemline-Sponsored 
Study 
Study 
0114 
(BPDCN) 
Study 0114 
(AML) 
Study 0214 
Study 
0314 
Total 
MedDRA Preferred Term 
(N=47) 
n (%) 
(N=49) 
(N=14) 
n (%) 
n (%) 
(N=15) 
n (%) 
(N=12 
5) n 
(%) 
At least 1 TEAE 
47 (100.0) 
49 (100.0) 14 (100.0) 
15 (100.0) 
125 (100.0) 
Alanine aminotransferase 
increased 
30 (63.8) 
30 (61.2) 
6 (42.9) 
3 (20.0)69 
(55.2) 
Aspartate aminotransferase 
increased 
28 (59.6) 
33 (67.3) 
5 (35.7) 
2 (13.3)68 
(54.4) 
Hypoalbuminemia 
26 (55.3) 
30 (61.2) 
7 (50.0) 
3 (20.0)66 
(52.8) 
Fatigue 
21 (44.7) 
27 (55.1) 
6 (42.9) 
7 (46.7)61 
(48.8) 
Nausea 
21 (44.7) 
26 (53.1) 
6 (42.9) 
5 (33.3)58 
(46.4) 
Oedema peripheral 
24 (51.1) 
19 (38.8) 
3 (21.4) 
9 (60.0)55 
(44.0) 

 
 
         
             
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Stemline-Sponsored 
Study 
Study 
0114 
(BPDCN) 
Study 0114 
(AML) 
Study 0214 
Study 
0314 
Total 
Pyrexia 
21 (44.7) 
22 (44.9) 
5 (35.7) 
6 (40.0)54 
(43.2) 
Thrombocytopenia 
23 (48.9) 
11 (22.4) 
6 (42.9) 
4 (26.7)44 
(35.2) 
Headache 
12 (25.5) 
16 (32.7) 
4 (28.6) 
6 (40.0)38 
(30.4) 
Hyperglyc1emia 
17 (36.2) 
17 (34.7) 
3 (21.4) 
1 (6.7)38 
(30.4) 
Chills 
16 (34.0) 
12 (24.5) 
5 (35.7) 
3 (20.0)36 
(28.8) 
Dyspnea 
6 (12.8) 
18 (36.7) 
3 (21.4) 
9 (60.0)36 
(28.8) 
Anemia 
11 (23.4) 
13 (26.5) 
3 (21.4) 
7 (46.7)34 
(27.2) 
Hypotension 
13 (27.7) 
16 (32.7) 
2 (14.3) 
3 (20.0)34 
(27.2) 
Decreased appetite 
12 (25.5) 
15 (30.6) 
2 (14.3) 
4 (26.7)33 
(26.4) 
Weight increased 
18 (38.3) 
11 (22.4) 
3 (21.4) 
1 (6.7)33 
(26.4) 
Vomiting 
8 (17.0) 
14 (28.6) 
3 (21.4) 
5 (33.3)30 
(24.0) 
Diarrhea 
7 (14.9) 
13 (26.5) 
3 (21.4) 
6 (40.0)29 
(23.2) 
Dizziness 
8 (17.0) 
12 (24.5) 
3 (21.4) 
6 (40.0)29 
(23.2) 
Back pain 
12 (25.5) 
10 (20.4) 
2 (14.3) 
4 (26.7)28 
(22.4) 
Constipation 
11 (23.4) 
10 (20.4) 
2 (14.3) 
4 (26.7)27 
(21.6) 

 
 
         
             
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Stemline-Sponsored 
Study 
Study 
0114 
(BPDCN) 
Study 0114 
(AML) 
Study 0214 
Study 
0314 
Total 
Capillary leak syndrome 
9 (19.1) 
10 (20.4) 
2 (14.3) 
4 (26.7)25 
(20.0) 
Hypokalemia 
10 (21.3) 
11 (22.4) 
1 (7.1) 
3 (20.0)25 
(20.0) 
Febrile neutropenia 
5 (10.6) 
17 (34.7) 
1 (7.1) 
023 (18.4) 
Insomnia 
7 (14.9) 
8 (16.3) 
2 (14.3) 
6 (40.0)23 
(18.4) 
Cough 
3 (6.4) 
13 (26.5) 
2 (14.3) 
4 (26.7)22 
(17.6) 
Hypocalcemia 
11 (23.4) 
8 (16.3) 
1 (7.1) 
2 (13.3)22 
(17.6) 
Tachycardia 
7 (14.9) 
10 (20.4) 
2 (14.3) 
2 (13.3)21 
(16.8) 
Pain in extremity 
5 (10.6) 
8 (16.3) 
1 (7.1) 
5 (33.3)19 
(15.2) 
Hyponatremia 
9 (19.1) 
7 (14.3) 
1 (7.1) 
1 (6.7)18 
(14.4) 
Neutropenia 
8 (17.0) 
7 (14.3) 
2 (14.3) 
1 (6.7)18 
(14.4) 
Anxiety 
9 (19.1) 
4 (8.2) 
0 
4 (26.7)17 
(13.6) 

 
 
         
             
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Hypertension 
10 (21.3) 
5 (10.2) 
0 
2 (13.3)17 
(13.6) 
Epistaxis 
3 (6.4) 
11 (22.4) 
1 (7.1) 
1 (6.7)16 
(12.8) 
Blood alkaline phosphatase 
increased 
5 (10.6) 
9 (18.4) 
1 (7.1) 
015 (12.0) 
Blood lactate dehydrogenase 
increased 
5 (10.6) 
8 (16.3) 
2 (14.3) 
015 (12.0) 
Abdominal pain 
4 (8.5) 
5 (10.2) 
2 (14.3) 
3 (20.0)14 
(11.2) 
Blood creatinine increased 
6 (12.8) 
6 (12.2) 
2 (14.3) 
014 (11.2) 
Hypoxia 
3 (6.4) 
6 (12.2) 
1 (7.1) 
3 (20.0)13 
(10.4) 
Myalgia 
1 (2.1) 
8 (16.3) 
2 (14.3) 
2 (13.3)13 
(10.4) 
 
 
In response to the initial case of Grade 5 CLS, which occurred in a patient with BPDCN treated 
at the 7 mcg/kg dose level early in the clinical program in Study SL-401-0114, all tagraxofusp 
protocols were amended to exclude patients with left ventricular ejection fraction (LVEF) below 
the institutional lower limit of normal, and specify that tagraxofusp infusions should be withheld 
for patients who have an increase in body weight during the dosing period or other potential 
early evidence of CLS. After the occurrence of Grade 4 CLS, additional precautions were 
implemented in all tagraxofusp protocols, including instructions that tagraxofusp dosing cease 
within a given cycle in the setting of substantial albumin reductions or · Grade 3 transaminase 
elevations. The second Grade 5 case of CLS occurred in a patient with AML treated with 
tagraxofusp at the 16 mcg/kg dose level, in Study STML-401-0114, a dose level above the MTD 
determined in that study of 12 m/kg/day. 
 
2.3.3 
Carcinogenesis, Mutagenesis, and Impairment of Fertility 
 
At present, reproductive and developmental toxicology studies have not been performed for 
tagraxofusp; consequently, it is recommended that females of childbearing potential and 
sexually active males use adequate birth control during study participation and for 2 months 
after the last dose of tagraxofusp. 
 
3.0 Patient Eligibility 
 
3.1 
Inclusion criteria 
1. Eligible patients will be aged >/= 18 years. Pediatric patients age 2 years and older will be 
considered on a case by case basis. 
2. Diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) according to 
WHO classification or confirmed by hematopathology.24,25 
3. The patients must be in partial response or better (see Appendix A.). 
4. > 30 days post-transplant without active or chronic infections. 
5. Karnofsky performance status >/= 60%; Lansky >/= 60 (see Appendices B. and C.). 

 
 
         
             
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6. LVEF >/= institutional lower limit of normal by MUGA scan or echocardiogram within 30 days 
of first protocol treatment. 
7. Pulmonary function: DLCO, FEV1, FVC > 40% of predicted value (corrected for hemoglobin) 
within 3 months of registration. 
8. Adequate organ function: 
a. 
Serum creatinine </= 1.5 mg/dL (133 mmol/L). 
b. 
Serum albumin >/= 3.2 g/dL (or >/= 32 g/L) without IV albumin within the previous 72 
hours. 
c. 
Bilirubin </= 1.5 x the upper limit of normal ([ULN] except patients with Gilbert syndrome 
in whom bilirubin level of > 1.5x ULN will be allowed). 
d. 
AST and ALT </= 2.5 times ULN. 
e. 
Hemoglobin >/= 8 g/dL with or without transfusion in the last 7 days. 
f. 
Absolute neutrophil count (ANC) >/= 1000 without GCSF or GMCSF in the last 2 weeks 
prior to screening. 
g. 
Platelets >/= 50,000/mL. 
9. For allo-HCT, no >/= grade 2 visceral (gut or liver) acute GVHD and no >/= grade 3 or any 
other acute GVHD (Patients with chronic GVHD will be allowed at the discretion of the 
investigator). 
10. Patient agrees to use acceptable contraceptive methods for the duration of time in the study, 
and to continue to use acceptable contraceptive methods for 2 months after the last 
tagraxofusp infusion. 
11. Woman of child bearing potential (WOCBP) with a negative serum or urine pregnancy test 
within 14 days of tagraxofusp treatment. 
12. Patient or patient’s legal representative, parent(s) or guardian able to sign informed consent. 
13. The patient can adhere to the study visit schedule and other protocol requirements, 
including follow-up for survival assessment. 
 
3.2 
Exclusion criteria 
1. The patient has persistent clinically significant non-hematologic toxicities >/= Grade 2 
(excluding alopecia, nausea, and fatigue). 
2. Evidence of CNS involvement. 
3. Uncontrolled and active pulmonary disease. 
4. Requirement for oxygen treatment. 
5. Receiving chemotherapy, radiotherapy or other anti-cancer therapy within 14 days of first 
dose of study drug. There must be at least a 6-week interval from the last immunotherapy 
therapy. 
6. Uncontrolled infection. 
7. HIV/Hepatitis B and/or C. 
8. Any history of invasive malignancy in the last 2 years excluding any malignancy such as 
cervical cancer or skin cancer (excluding melanoma) that is considered cured at the time of 
screening. 
9. Pregnant or breast-feeding woman. 
10. Patient has uncontrolled intercurrent illness or medical/psychiatric condition that would limit 
compliance with study requirements or that would in the Investigator’s opinion place the 
patient at an unacceptably high risk for toxicities. 
11. Clinical significant cardiopulmonary disease including uncontrolled or NYHA class 3 or 4 
congestive heart failure, uncontrolled angina, uncontrolled hypertension, uncontrolled 
arrhythmia, myocardial infarction or stroke within 6 months of first protocol treatment or QTc 
> 480 ms. 

 
 
         
             
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4.0 Treatment Plan 
 
4.1 
Treatment initiation 
 
Between Day + 45 and Day +180 post HCT if the patient meets the eligibility criteria. 
 
4.2 
Treatment duration 
- 
Patients in CRi or PR post-transplant will be treated until disease progression or 
unacceptable toxicity. 
- 
Patients in CR or CRc post-transplant will be treated for 24 cycles, then: 
o 
Patients who are MRD-positive or have different characteristics that, in the opinion of the 
investigator, put them at a high-risk o relapse, may continue to receive treatment as long 
as they continue to derive benefit and remain in remission. 
o 
Patients who are MRD-negative and don’t have other characteristics indicative of 
high-risk of relapse will stop treatment after 24 cycles, unless the Investigator has a 
reason to continue treatment (for example, conversion from MRD-positive to 
MRD-negative only shortly before the 24th cycle). 
 
4.3 
Pre-medication 
 
Approximately 60 minutes prior to receiving tagraxofusp. 
· 
Acetaminophen 650 mg PO 
· 
Diphenhydramine 50 mg IV 
· 
Methylprednisolone 50 mg IV (or equivalent dosage of another corticosteroid) 
· 
Ranitidine 50 mg IV (or equivalent dosage of another H2-histamine antagonist) 
· 
Ondansetron 16 mg IV 
 
4.4 
Dose and schedule 
 
First three patients: 
· 
Cycles 1-4: Tagraxofusp 9 mcg/kg IV on Days 1, 2, and 3. 
· 
Cycles 5 and beyond: Tagraxofusp 12 mcg/kg IV on Days 1 and 2 (if no unacceptable 
toxicities at the 9 ug/kg/day IV dose, as defined in the statistical section). 
 
Patient number 4 and beyond: 
· 
Cycles 1-4: Tagraxofusp 12 ug/kg/day IV on Days 1, 2, and 3. 
· 
Cycles 5 and beyond: Tagraxofusp 12 ug/kg/day IV on Days 1 and 2. 
 
Cycle Length: 28 days 
 
During a 28-day cycle, if the patient experiences related non-hematological toxicity with 
resolution to Grade <1 or baseline by day 28, the tagraxofusp dose may be continued during the 
next cycle at the same dose. 
 
Otherwise tagraxofusp-related non-hematological toxicity not resolved to Grade  ≤ 1 or baseline 
by day 28, the start of the next cycle will be delayed until resolution to Grade  ≤ 1 or baseline up 
to a maximum of additional 28 (56 total) days. 

 
 
         
             
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After this treatment delay dosing may be continued during the next cycle at same dose. 
4.5 
Route and Administration 
 
Tagraxofusp is administered by IV infusion via syringe pump over 15 minutes. Prior to infusion, 
venous access should be established and maintained with sterile 0.9% Sodium Chloride 
Injection, USP. The total infusion time will be controlled using a syringe pump to deliver the 
entire dose over 15 minutes. 
 
Attach the tagraxofusp syringe containing the patient’s dose to one port and the saline flush 
syringe to the other port of a Smith’s Medical Y connector or equivalent. Clamp off the ports until 
needed. Attach the opposite end of the Y connector to the microbore tubing. Attach an in- line 
filter to the opposite end of the microbore tubing. Prime the saline port of the Y connector up to 
the intersection and clamp shut until the saline flush is required. Next, prime the entire 
administration set up with the diluted tagraxofusp dose so that it is ready to attach inline. 
When the tagraxofusp syringe is empty, remove it from the pump and place the saline flush 
syringe in the syringe pump. Open the clamp on the saline flush side of the Y connector and 
resume infusion via the syringe pump at the pre-specified flow. Note that the flush syringe will 
not be emptied entirely at the end of the 15-minute infusion, since it is just intended to push 
remaining tagraxofusp out of the infusion line to complete drug delivery. 
The dose of tagraxofusp will be dependent upon the patient’s body weight in kg. The dose for 
subsequent cycles is to be recalculated only if there is a 10% change in body weight from 
baseline. The aliquot is calculated from the mg/kg dose x patient weight in kg (all patient doses 
are calculated in mg/kg body weight). Dose changes should only occur once a cycle has been 
completed. Intra-cycle dose modifications are not permitted. 
 
Inpatient admission for cycle 1 only (day 1 or one day before day 1). After cycle 1, Tagraxofusp 
can be administered in the inpatient setting or in a suitable outpatient ambulatory care setting 
that is equipped for intensive monitoring of patients with hematopoietic malignancies 
undergoing treatment, per the discretion of the investigator and institutional guidelines and 
capabilities. 
 
Observation post-dosing should continue until it is clear that the patient does not have 
evidence/symptoms of capillary leak syndrome (e.g., no weight gain, edema, hypotension, or 
decrease in albumin) or hypersensitivity reaction. Participants will be monitored as described in 
Section 5.0, Evaluations During Study. 
 
Supportive care is permitted according to standard institutional/department of MD Anderson 
Stem Cell Transplantation and Cellular Therapy protocols. 
 
4.6 
Dose modifications for tagraxofusp related hematological toxicity 
 
It is often very challenging to differentiate disease-related from treatment-related hematological 
toxicities in patients with BPDCN. Patients with neutropenia, anemia, or thrombocytopenia as a 
consequence of their disease do not require treatment interruptions for myelosuppression. 
Dose-interruptions in these patients should be considered on a case-by-case basis and 
discussed with the PI. 
 
 
 

 
 
         
             
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4.7 
Discontinuation of treatment 
 
Treatment will continue until maximal duration of maintenance therapy is reached (as specified 
in Section 4.0, Treatment Duration), or the occurrence of any of the following events: 
· 
Disease progression 
· 
Adverse event(s) that, in the judgment of the Investigator/Medical Monitor, may cause 
severe or permanent harm or which rule out continuation of maintenance study drug. 
· 
Graft failure 
· 
Development of grade III-IV acute GVHD 
· 
Development of severe chronic GVHD 
· 
Suspected pregnancy 
· 
Inability to start planned cycle of tagraxofusp within 56 days of intended start date of each 
cycle. 
· 
Major violation of the study protocol (to include subject noncompliance with study 
medications or protocol-specified procedures) at the discretion of the PI 
 
4.8 Procedures During Dosing Period 
 
Monitor vital signs and check albumin, transaminases, and creatinine prior to preparing each 
dose of tagraxofusp. During each cycle, testing and procedures that may result in withholding of 
a scheduled tagraxofusp infusion, largely based on unresolved manifestations of fluid retention 
and/or other relevant acute toxicities during daily dosing, are described below. Details are 
presented in Table 3. 
 
Table 3: Recommended Dose Modifications 
 
Parameter 
Severity Criteria 
Dose Modification 
Serum albumin 
Serum albumin < 3.5 g/dL or reduced 
≥ 0.5 g/dL from value measured prior 
to initiation of the current cycle 
See CLS Management 
Guidelines (Appendix D.) 
Body weight 
Body weight increase ≥1.5 kg over 
pretreatment weight on prior treatment 
day 
See CLS Management 
Guidelines (Appendix D.) 
Aspartate 
aminotransferase 
(AST) or alanine 
aminotransferase 
ALT) 
ALT or AST increase > 5 times the 
upper limit of normal 
Withhold tagraxofusp until 
transaminase elevations are 
≤ 2.5 times the upper limit of 
normal. 
Serum creatinine 
Serum creatinine > 1.8 mg/dL (159 
micromol/L) or creatinine clearance 
< 60 mL/minute 
Withhold tagraxofusp until 
serum creatinine resolves to 
≤ 1.8 mg/dL (159 micromol/L) 
or creatinine clearance ≥ 60 
mL/minute. 
Systolic blood 
pressure 
Systolic blood pressure ≥ 160 
mmHg or ≤ 80 mmHg 
Withhold tagraxofusp until 
systolic blood pressure is < 160 
mmHg or > 80 mmHg. 
Heart rate 
Heart rate ≥ 130 bpm or ≤  40 bpm 
Withhold tagraxofusp until heart 
rate is < 130 bpm or > 40 bpm. 
Body temperature 
Body temperature ≥ 38°C 
Withhold tagraxofusp until body 
temperature is < 38°C. 

 
 
         
             
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Parameter 
Severity Criteria 
Dose Modification 
Hypersensitivity 
reactions 
Mild or moderate 
Withhold tagraxofusp until 
resolution of any mild or 
moderate hypersensitivity 
reaction. Resume tagraxofusp 
at the same infusion rate. 
Severe or life-threatening 
Discontinue tagraxofusp 
permanently. 
 
Except in conditions specified above, tagraxofusp may be re-administered subsequently in the 
same cycle, pending normalization of the abnormalities and pending evidence of stabilization of 
the underlying clinical conditions resulting in these abnormalities. Postponed doses may be 
administered within a 10-day period following the initial day of treatment within a cycle. 
 
In the setting of findings possibly consistent with infection, tagraxofusp may be administered 
pending resolution, provided that an appropriate evaluation for infectious etiologies has been 
undertaken, and provided that the investigator determines that there is minimal likelihood of 
uncontrolled systemic infection including sepsis; this may occur on the same day as the 
temperature elevation, or on subsequent days. 
 
4.9 
Management of Specific Toxicities Capillary leak syndrome (CLS) 
 
Capillary leak syndrome (CLS) is associated with vascular endothelial injury related to 
tagraxofusp administration and often occurs 3-8 days after initiation of treatment. 
See Appendix D. for management of CLS and associated symptoms (hypoalbuminemia, 
edema, weight gain and hypotension). 
In the setting of delays secondary to findings consistent with CLS (i.e., in the setting of 
resolved hypotension, tachycardia, increased weight, or albumin reductions of a magnitude 
lower than those warranting withholding of tagraxofusp for the duration of a given cycle), 
subsequent tagraxofusp is to be administered on days subsequent to the identification of the 
abnormality (not the same day), pending determination by the investigator that there is 
no/minimal evidence of ongoing CLS and pending discussion with the PI. 
 
5.0 Evaluation During Study 
Every effort will be made to adhere to the schedule of events and all protocol requirements. 
Variations in schedule of events and other protocol requirements that do not affect the rights 
and safety of the patient will not be considered as deviations. Such variations may include 
laboratory assessments completed outside of schedule and occasional missed required 
research samples. Missed samples for correlative studies will not constitute protocol deviations. 
 
 
 

 
 
         
             
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      Table of Evaluations 
 
 
 
 
Pre-
treatment2  
 
Pre-
Infusion 
 
Cycles 1-61 
 
Cycles 7-12 
 
Cycles 13+ 
Day 1 
Day 2 
Day 3 
Day 7 Day 155  Day 1 
Day 2 Day 155 Day 1 
Day 2 
Physical 
exam 
X3 
 
X4 
 
 
X 
X 
X4 
  
 
X4 
 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lab tests 
X6 
X7 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
Pregnancy 
test 
X8 
 
 
 
 
 
 
 
 
 
 
 
12-lead 
EKG 
X 
X9 
X 
 
 
 
 
 
 
 
 
 
ECHO, 
PFTs 
X 
 
 
 
 
 
 
 
 
 
 
 
Bone 
Marrow 
aspiration/
biopsy 
 
X10 
 
 
 
 
 
 
 
 
 
 
 
CT (chest, 
abdomen, 
pelvis) 
X 
 
 
 
 
 
 
 
 
 
 
 
Lumbar 
puncture 
X11 
 
 
 
 
 
 
 
 
 
 
 
AE, SAE 
Monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
1 Cycle 1: Administered as inpatient. While in the hospital, the observation post-dosing should continue, as clinically 
indicated, until it is clear that the patient doesn’t have evidence/symptoms of capillary leak syndrome (e.g., no 
weight gain, edema, hypotension, or decrease in albumin) or hypersensitivity reaction. At discharge after Cycle 1: 
At least once/week for 2 weeks: Physical exam, vital signs, weight, AE and SAE monitoring, clinical lab tests: CBC 
w/diff; serum electrolytes and chemistry (including albumin), and coagulation parameters. 
2 Pre-treatment evaluations: Within 30 days of enrollment unless otherwise specified. 
3 Physical exam, pre-treatment: Include detailed skin examination (+/- skin biopsy, as clinically indicated). 
4 Physical exam, Cycles 1-6,Cycles 7-12 and Cycle 13+ Day 1: Within 48 hours of tagraxofuspinfusion. 
5 Day 15: (+/-3 days). 
6 Pre-treatment labs: CBC with differential, serum chemistries including electrolytes, renal function tests, coagulation 
parameters, albumin, and liver function tests, lactate dehydrogenase (LDH), uric acid HIV/Hepatitis B and/or C. 
7 Pre-infusion labs: CBC with differential, serum electrolytes and chemistry (including albumin), renal function 
tests, and liver function tests, lactate dehydrogenase (LDH), uric acid and coagulation parameters. 
8 Serum or urine pregnancy test for women of child bearing potential (WOCBP), within 14 days of starting treatment. 
9 12-lead EKG: Before infusion, Cycle 1 only. 
10 Bone marrow aspiration and biopsy for pathologic review, immunophenotyping/flowcytometry, 
cytogenetic, molecular, and FISH analysis 
11 Lumbar puncture for CSF analysis with routine CSF studies, cytology, and flow cytometry (optional, if not done 
previously and has history of CNS involvement). 
 
 
5.1 Disease specific monitoring 
Disease specific monitoring will be performed per Stem Cell Transplantation and Cellular 
Therapy guidelines. 
 

 
 
         
             
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5.2 
Evaluations during follow up 
 
All patients who do not discontinue study drug for toxicity will need to be followed for 30 days 
post-discontinuation to address any late developing toxicities which may occur. This follow up 
will cease when patients start a new therapy if prior to the 30-day follow up interval. 
 
5.3 
Duration of follow up 
Participants will be followed for one year after removal from protocol therapy with either 
clinic visit or a phone call, or until death, whichever occurs first. Participants removed from 
protocol therapy for unacceptable adverse event(s) will be followed until resolution or 
stabilization of the adverse event. 
 
5.4 
Outside Physician Participation During Treatment 
 
Starting Cycle 2, post tagraxofusp infusion: Laboratory tests and follow up visit can be 
performed locally and results sent to MDACC.  
 
5.4.1 MDACC Physician communication with the outside physician is required prior to the 
patient returning to the local physician.  This will be documented in the patient record. 
 
5.4.2  A letter to the local physician outlining the patient's participation in a clinical trial will 
request local physician agreement to supervise the patient's care (Appendix E.). 
 
5.4.3 Protocol required evaluations outside MDACC will be documented by telephone, fax 
or e-mail.  Fax and/or e-mail will be dated and signed by the MDACC physician, 
indicating that they have reviewed it. 
 
5.4.4 Changes in drug dose and/or schedule must be discussed with and approved by the 
MDACC physician investigator, or their representative prior to initiation, and will be 
documented in the patient record. 
 
5.4.5 A copy of the informed consent, protocol abstract, treatment schema and evaluation 
during treatment will be provided to the local physician 
 
5.4.6 Documentation to be provided by the local physician will include drug administration 
records, progress notes, reports of protocol required laboratory and diagnostic studies 
and documentation of any hospitalizations. 
 
5.4.7 The home physician will be requested to report to the MDACC physician investigator 
all life threatening events within 24 hours of documented occurrence. 
 
5.4.8 Patients will return to MDACC for each 28-day tagraxofusp infusion cycle.

 
 
         
             
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6.0 
Adverse Events and Reporting Requirements 
 
An adverse event (AE) is the appearance or worsening of any undesirable sign, symptom, or 
medical condition occurring after starting the study drug even if the event is not considered to 
be related to study drug. Medical conditions/diseases present before starting study drug are 
only considered adverse events if they worsen after starting study drug. Abnormal laboratory 
values or test results constitute adverse events only if they induce clinical signs or symptoms, 
are considered clinically significant, or require therapy. 
 
The investigator (or physician designee) is responsible for verifying and providing source 
documentation for all adverse events and assigning the attribution for all adverse events for 
subjects enrolled. 
For the purpose of this study, the investigational component of the treatment plan is tagraxofusp 
(SL-401). Therefore, serious and unexpected adverse events occurring from the time of infusion 
of tagraxofusp up to 30 days of the last infusion of tagraxofusp, as defined below, will be 
reported according to MDACC policy and procedures below. The end of active treatment is the 
completion of the last infusion of tagraxofusp. Serious adverse events must be followed until 
clinical recovery and laboratory test have returned to baseline, progression of the event has 
stabilized, or there has been acceptable resolution of the event. 
 
AEs will graded according to the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.0. A copy of CTCAE version 5.0 can be downloaded from the CTEP website 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50 
 
Grade – Severity of the adverse event. Grades were developed using the following 
guidelines: 
 
Grade 0 – No adverse event or within normal limits 
 
1 – Mild adverse event 
2 – Moderate adverse event 
3 – Severe adverse event 
4 – Life-threatening or disabling adverse event 
5 – Fatal adverse event 
 
Abnormal laboratory values not included in the CTCAE guidelines will be defined per protocol. 
Time for AE Collection 
Adverse events will be collected from the start of the study drug until 30 days after the last 
infusion of tagraxofusp. 
Adverse Event Reporting 
 
The Investigator or physician designee is responsible for verifying and providing source 
documentation for all adverse events, and assigning attribution for each event on all subjects 
enrolled on this study. 

 
 
         
             
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Data collection 
 
Collection of adverse events will reflect the onset and resolution date and maximum grade. 
Intermittent events should be labeled as such and followed until resolution. If a patient is taken 
off study while an event still ongoing, this will be followed until resolution unless another 
therapy is initiated. Pre-existing medical conditions will be recorded only if an exacerbation 
occurs during the active treatment period. 
 
Patients will be registered in MD Anderson’s Clinical Trial Management System, OnCore. 
 
Adverse events and all protocol specific data will be entered into the electronic case report form 
(REDCap). 
 
Events not to be considered adverse events in this study are those related to original disease or 
expected in the post-allogeneic transplant period. 
 
Isolated changes in laboratory parameters such as electrolyte, magnesium and metabolic 
imbalances, uric acid changes, elevations of LDH and alkaline phosphatase will not be 
monitored. 
 
Concomitant medications 
 
Patients treated on this protocol will require supportive care treatment (concomitant 
medications). These medications are considered standard of care and have no scientific 
contribution to the protocol; therefore no data will be captured on various medications needed or 
their side effects. All antiviral therapy will be captured in the medical record. 
 
6.1 
Serious Adverse Event (SAE) Reporting 
 
An adverse event or suspected adverse reaction is considered “serious” if, in the view of either 
the investigator or the sponsor, it results in any of the following outcomes: 
 
· 
Death 
· 
A life-threatening adverse drug experience – any adverse experience that places the 
patient, in the view of the initial reporter, at immediate risk of death from the adverse 
experience as it occurred. It does not include an adverse experience that, had it occurred in 
a more severe form, might have caused death. 
· 
Inpatient hospitalization or prolongation of existing hospitalization 
· 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions. 
· 
A congenital anomaly/birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse (21 CFR 312.32). 
 

 
 
         
             
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· 
Important medical events as defined above, may also be considered serious adverse 
events. Any important medical event can and should be reported as an SAE if deemed 
appropriate by the Principal Investigator or the IND Sponsor, IND Office. 
· 
All events occurring during the conduct of a protocol and meeting the definition of a SAE 
must be reported to the IRB in accordance with the timeframes and procedures outlined in 
“The University of Texas M. D. Anderson Cancer Center Institutional Review Board Policy 
for Investigators on Reporting Serious Unanticipated Adverse Events for Drugs and 
Devices”. Unless stated otherwise in the protocol, all SAEs, expected or unexpected, must 
be reported to the IND Office, regardless of attribution (within 5 working days of knowledge 
of the event). 
· 
All life-threatening or fatal events, that are unexpected, and related to the study drug, must 
have a written report submitted within 24 hours (next working day) of knowledge of the event 
to the Safety Project Manager in the IND Office. 
· 
OnCore, will be utilized for safety reporting to the IND Office and MDACC IRB. 
· 
Serious adverse events will be captured from the time of the first protocol-specific 
intervention, until 30 days after the last dose of drug, unless the participant withdraws 
consent. Serious adverse events must be followed until clinical recovery is complete and 
laboratory tests have returned to baseline, progression of the event has stabilized, or there 
has been acceptable resolution of the event. 
· 
Additionally, any serious adverse events that occur after the 30 day time period that are 
related to the study treatment must be reported to the IND Office. This may include the 
development of a secondary malignancy. 
 
Reporting to FDA: 
 
· 
Serious adverse events will be forwarded to FDA by the IND Sponsor (Safety Project 
Manager IND Office) according to 21 CFR 312.32. A copy of this form will be submitted to 
Stemline Therapeutics at the same time it is submitted to the IND Office. 
 
 
It is the responsibility of the PI and the research team to ensure serious adverse events are 
reported according to the Code of Federal Regulations, Good Clinical Practices, the protocol 
guidelines, the sponsor’s guidelines, and Institutional Review Board policy. 
 
 

 
 
         
             
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7.0 Criteria for Removal from the Study 
 
Participants will be removed from the study when any of the following criteria apply: 
1. Patient withdrawal of the informed consent. 
2. Patient's inability or unwillingness to have follow-up visits and/or laboratory tests required by 
this protocol. 
3. General or specific circumstances, which render the participant unacceptable for further 
treatment in the judgment of the treating investigator. 
4. An unexpected toxicity that is deemed unacceptable by the study chairman. 
5. Disease progression. 
6. After one year of treatment completion. 
7. Death. 
8. Lost to follow up 
8.0 Statistical Considerations 
 
Type of study: Open label, single-arm, single center, Phase 2 clinical trial 
 
Number of patients planned: 20 
 
Expected accrual rate: 5-10 patients/year 
 
Toxicity monitoring 
 
Continuous monitoring of toxicity will be performed in all 20 patients. The first 3 patients will be 
treated with 9 mcg/kg in first 4 cycles. From cycle 5 and beyond in the first 3 patients, the dose 
will be 12 ug/kg/day. All subsequent patients will be treated with 12 ug/kg/day. Unacceptable 
toxicities are defined as tagraxofusp-related toxicities which prevent initiation of Cycle 2 of 
therapy (Any adverse event ³ grade 3 that is both a) considered related to tagraxofusp, and b) 
does not resolve to ≤ grade 2 after a maximum delay of 56-days). Assuming a prior beta 
distribution of (0.4, 1.6), corresponding to an unacceptable toxicity rate of 30%, treatment will 
terminate if the Pr (dt > 0.20 |data) > 0.95, where dt is the toxicity rate attributable to the 
tagraxofusp treatment. The decision rule for terminating for toxicity is presented in Table 4 and 
the software used for this Bayesian toxicity monitoring rule is Multc Lean version 2.1.0. The 
operating characteristics for this rule are presented in Table 5. The method used to produce the 
decision rule and operating characteristics was designed by Thall, Simon, and Estey 
26, 27 and 
extended by Thall and Sung.
28
 

 
 
         
             
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Table 4 Stopping criteria 
 
Total Patients 
Enrolled 
Stopping Condition 
(# of patients experiencing 
unacceptable toxicities) 
3-4 
3-4 
5-8 
4-8 
9-11 
5-11 
12-14 
6-14 
15-18 
7-18 
19 
8-19 
20 
Patient enrollment ends 
 
 
Table 5 Operating characteristics 
 
True % of 
DLTs 
Pr (stopping 
early) 
Average # of 
patients 
treated 
0.05 
0.00 
20 
0.10 
0.01 
20 
0.20 
0.11 
19 
0.30 
0.38 
16 
0.40 
0.70 
12 
0.50 
0.91 
9 
 
Analysis 
 
Demographic and baseline characteristics will be summarized. Categorical measures will be 
summarized using frequencies and percentages while continuous variables will be summarized 
using mean, standard deviation, median, minimum, and maximum. 

 
 
         
             
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The primary endpoint of the study is the tolerability of tagraxofusp post-SCT, where tolerability is 
defined as receipt of at least 75% of planned tagraxofusp doses in at least 4 cycles of therapy. 
The following table shows the exact 95% confidence intervals for different percentages of 
patients, out of 20 patients, experiencing tolerability: 
 
 
Patients experiencing tolerability 
95% Exact 
Number 
Percentage 
Confidence Interval 
2 
10% 
1.2% - 31.7% 
5 
25% 
8.7% - 49.1% 
10 
50% 
27.2% - 72.8% 
15 
75% 
50.9% - 91.3% 
 
The percentage of patients considered ‘tolerating’ by this definition will be presented along with 
the associated 95% exact confidence interval. 
 
PFS is defined as the duration from treatment start date to date of disease progression or 
death. Patients who are still alive at the end of the study with no evidence of disease will be 
censored. OS is defined as the time from treatment start date to death. Patients who are still 
alive at the end of the study will be censored. PFS and OS will be estimated using the 
Kaplan-Meier method. Median PFS and OS as well as rates with corresponding 95% confidence 
intervals will be presented. 
 
Summary Reports 
The Investigator is responsible for completing a toxicity/tolerability summary report, and 
submitting it to the IND Office Medical Affairs and Safety Group, for review and approval. This 
should be submitted after the first 3 evaluable patients, complete 1 cycle of study treatment, and 
every 2-3 evaluable patients, thereafter, following Table 4 stopping criteria guidelines. 
For tolerability, an updated summary report should be submitted every 2-5 patients complete 4 
cycles of study therapy, in accordance to the table located in the “Analysis” section of the 
protocol. 
 
A copy of the toxicity summary should be placed in the Investigator’s Regulatory Binder under 
“sponsor correspondence”. 

 
 
         
             
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9.0 References 
 
1. 
Pagano L, Valentini CG, Pulsoni A, et al. Blastic plasmacytoid dendritic cell neoplasm with 
leukemic presentation: an Italian multicenter study. Haematologica 2013; 98(2): 239-46. 
 
2. 
Facchetti F, Ungari M, Marocolo D, Lonardi S, Vermi W. Blastic plasmacytoid dendritic cell 
neoplasm Hematology Meeting Reports 2009; 3(3): 1-3. 
 
3. 
Sapienza MR, Fuligni F, Agostinelli C, et al. Molecular profiling of blastic plasmacytoid 
dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB 
pathway inhibition. Leukemia 2014; 28(8): 1606-16. 
 
4. 
Jardin F, Ruminy P, Parmentier F, et al. TET2 and TP53 mutations are frequently observed 
in blastic plasmacytoid dendritic cell neoplasm. British journal of haematology 2011; 153(3): 
413-6. 
 
5. 
Pagano L, Valentini CG, Grammatico S, Pulsoni A. Blastic plasmacytoid dendritic cell 
neoplasm: diagnostic criteria and therapeutical approaches. British journal of haematology 
2016; 174(2): 188-202. 
 
6. 
Julia F, Petrella T, Beylot-Barry M, et al. Blastic plasmacytoid dendritic cell neoplasm: 
clinical features in 90 patients. The British journal of dermatology 2013; 169(3): 579-86. 
 
7. 
Facchetti F. Plasmacytoid Dendritic Cell Neoplasms. Knowles Neoplastic Hematopathology 
In 3rd Edition (eds by Orazi, A, Weiss, LM, Foucar, KA & Knowles, DM) Lippincott Williams 
& Wilkins, Philadelphia 2013. 
 
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Dalle S, Beylot-Barry M, Bagot M, et al. Blastic plasmacytoid dendritic cell neoplasm: is 
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