Tagraxofusp in Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm or Acute Myeloid Leukemia

NCT02113982 | Completed Phase 1 Results DMC

• 1 other identifier: STML-401-0114
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 9

Brief Summary

This is a 4-stage, non-randomized, open-label, dose escalation and expansion, multicenter study. A cycle of therapy is 21 days. Stage 1 was a dose-escalation stage. During Stages 2-4, patients are treated at the MTD or maximum tested dose at which multiple DLTs are not observed during Stage 1.

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN); Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (2)

• MTD (Stage 1)

  Maximum tolerated dose (MTD) in both patients with BPDCN and AML. MTD defined as the highest dose level where less than 2/3 or 2/6 patients experienced a DLT

  21-day period after the first dose (cycle 1)

• CR Rate in First-line BPDCN (Stage 3, Pivotal Cohort)

  Complete response (CR) rate, defined as the percentage who achieved CR+ CR(clinical) with minimal residual skin abnormality (CRc) after treatment with Tagraxofusp. CR criteria according to Cheson BD et al, The International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-586: Marrow: normalization of blast percentage (≤5%). Peripheral blood: normalization of neutrophil count (≥ 1,000/µL) and platelet count (≥ 100,000/µL) - absence of leukemic blasts Skin: 100% clearance of all skin lesions from baseline; no new lesions in patients without lesions at baseline Nodal masses: regression to normal size on CT Spleen, liver: not palpable, nodules disappeared CRc criteria: all the above except for skin: marked clearance of all skin lesions from baseline; residual hyperpigmentation or abnormality with BPDCN identified on biopsy (or no biopsy performed)

  at pre-defined treatment cycle intervals from randomization up to disease progression, up to 3.5 years

Secondary Outcomes (5)

• CR Rate in First-line BPDCN, R/R BPDCN and AML

  at pre-defined treatment cycle intervals from randomization up to disease progression, up to 5 years

• Duration of CR in First-line BPDCN, R/R BPDCN and AML

  at pre-defined treatment cycle intervals from randomization up to disease progression, up to 5 years

• ORR in First-line BPDCN, R/R BPDCN and AML

  at pre-defined treatment cycle intervals from randomization up to disease progression, up to 5 years

• OS in First-line BPDCN, R/R BPDCN and AML

  From first infusion to treatment discontinuation when survival is assessed every 90 days up to end of follow-up or death, up to 5 years

• Bridge to SCT in First-line BPDCN, R/R BPDCN and AML

  at pre-defined intervals up to achievement of outcome enabling an SCT for a period, up to 5 years

Study Arms (3)

First-Line Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

EXPERIMENTAL

Intervention: Tagraxofusp

Drug: Tagraxofusp

Relapse/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

EXPERIMENTAL

Intervention: Tagraxofusp

Drug: Tagraxofusp

Acute Myeloid Leukemia

EXPERIMENTAL

Intervention: Tagraxofusp

Drug: Tagraxofusp

Interventions

Tagraxofusp DRUG

Also known as: SL-401

Acute Myeloid Leukemia; First-Line Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN); Relapse/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a diagnosis of AML (Protocol Stages 1 and 2) or BPDCN (Protocol Stages 1-4) according to WHO classification (AML; excluding acute promyelocytic leukemia \[APL, FAB M3\]) or confirmed by hematopathology (BPDCN) (Facchetti et al. 2008).
• The patient must meet one of the following (a) or (b) or (c):
• Has evidence of persistent or recurrent AML (Protocol Stages 1 and 2) in the peripheral blood and/or bone marrow that is refractory to, or has relapsed from, their most recent prior line of treatment.
• A prior line of treatment is considered an induction regimen if it involves an approved or investigational cytotoxic chemotherapy agent, biological agent, and/or hypomethylating agent administered alone or in a combination regimen, with the intent to induce robust cytoreduction (i.e., CR).
• The previous induction regimen may have been a SCT with intent to induce a CR.
• Consolidation and/or maintenance (including SCT) may have been given in CR/CRi, but are not counted as a line of treatment.
• Hydroxyurea will not be considered a prior line of treatment.
• Has previously untreated AML (Protocol Stages 1 and 2) and is considered to be at high risk for disease progression and/or is unlikely to derive more than transient benefit from standard therapy by having at least one of the following:
• Treatment-related AML, except if it is associated with favorable cytogenetics (e.g., inversion 16, t\[16;16\], t\[8;21\], t\[15;17\]), and not a candidate for SCT in their current disease state.
• AML with antecedent hematological disease (e.g., MDS, myelofibrosis, polycythemia vera) and not a candidate for SCT.
• Has histological and/or cytological evidence of BPDCN by pathologic assessment at the investigative site according to WHO classification (Facchetti et al. 2008) by a pathologist with expertise in hematologic malignancies, that can be measured for treatment response and is either:
• Previously untreated (i.e., first-line) (Protocol Stages 2-4).
• Persistent or recurrent in the peripheral blood, bone marrow, spleen, lymph nodes, skin, or other sites after previous treatment with at least 1 line of systemic therapy for BPDCN, e.g., stem cell transplant or chemotherapy (Protocol Stages 1, 2, and 4). A pathology specimen must be available for central pathology review for all BPDCN patients enrolled in Protocol Stages 2-4.
• The patient is ≥ 18 years old.
• The patient has an ECOG performance score (PS) of 0-2.

You may not qualify if:

• The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB M3).
• The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
• The patient has received treatment with another investigational agent within 14 days of study entry.
• The patient has previously received treatment with Tagraxofusp.
• The patient has an active malignancy and/or cancer history (excluding AML, BPDCN, or antecedent MDS) that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease.
• The patient has clinically significant cardiovascular disease (e.g., uncontrolled or any NYHA Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• The patient has uncontrolled, clinically significant pulmonary disease (e.g., COPD, pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study.
• The patient has known active or suspected CNS leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
• The patient is receiving immunosuppressive therapy - with the exception of low-dose prednisone (≤ 10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade ≥ 2 GVHD.
• The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, DIC, or psychiatric illness/social situations that would limit compliance with study requirements.
• The patient is pregnant or breast feeding.
• The patient has known positive status for human immunodeficiency virus (HIV) active or chronic Hepatitis B or Hepatitis C.
• The patient is oxygen-dependent.
• The patient has any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (9)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

H. Lee Moffiitt Cancer Center & Research Institute

Tampa, Florida, 12902, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center Presbyterian Shady Side

Pittsburgh, Pennsylvania, 15213, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Konopleva M, Pemmaraju N, Sweet KL, Stein AS, Rizzieri DA, Wang ES, Vasu S, Rosenblat T, Zuurman M, Gupta I, Lane AA. Hematopoietic effects of tagraxofusp in treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm. Cancer. 2026 Jan 1;132(1):e70243. doi: 10.1002/cncr.70243.

  PMID: 41486505 DERIVED

• Pemmaraju N, Sweet KL, Stein AS, Wang ES, Rizzieri DA, Vasu S, Rosenblat TL, Brooks CL, Habboubi N, Mughal TI, Kantarjian H, Konopleva M, Lane AA. Long-Term Benefits of Tagraxofusp for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm. J Clin Oncol. 2022 Sep 10;40(26):3032-3036. doi: 10.1200/JCO.22.00034. Epub 2022 Jul 12.

  PMID: 35820082 DERIVED

• Pemmaraju N, Lane AA, Sweet KL, Stein AS, Vasu S, Blum W, Rizzieri DA, Wang ES, Duvic M, Sloan JM, Spence S, Shemesh S, Brooks CL, Balser J, Bergstein I, Lancet JE, Kantarjian HM, Konopleva M. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019 Apr 25;380(17):1628-1637. doi: 10.1056/NEJMoa1815105.

  PMID: 31018069 DERIVED

MeSH Terms

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm; Leukemia, Myeloid, Acute

Interventions

tagraxofusp

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Leukemia; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leukemia, Myeloid

Limitations and Caveats

This study was limited by lack of randomization due to the ultra-rare nature of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Patients lacked established response criteria for BPDCN prior to STML-401-0114.

Results Point of Contact

• Title: Ira Gupta, MD
• Organization: Stemline Therapeutics, Inc.

clinicaltrials@menarinistemline.com

877-332-7967

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2014
• First Posted: April 15, 2014
• Study Start: September 1, 2014
• Primary Completion: February 1, 2020
• Study Completion: March 12, 2020
• Last Updated: August 1, 2024
• Results First Posted: August 1, 2024

Record last verified: 2024-07

Locations

US (9)