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Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)Phase 1/2NCT02113982

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

A Phase 1/2 study testing Tagraxofusp in people with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) and Acute Myeloid Leukemia (AML), run by Stemline Therapeutics, Inc. at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tagraxofusp
Could I receive a placebo?
No, everyone receives an active treatment
How many people
138 participants
Where
9 sitesUnited States
Study dates
Sep 2014to 12 Mar 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:
  • Left ventricular ejection fraction (LVEF) ≥ institutional lower limit of normal as measured by MUGA scan or 2-D ECHO within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead ECG
  • Serum creatinine ≤ 1.5 mg/dl
  • Serum albumin ≥ 3.2 g/dl
  • Bilirubin ≤ 1.5 mg/dl
  • AST and ALT ≤ 2.5 times the upper limit of normal (ULN)
  • If the patient is a woman of child bearing potential (WOCBP), she has had a negative serum or urine pregnancy test within 1 week prior to treatment.
  • The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.
  • The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
  • The patient (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study, and continue to use acceptable contraceptive methods for 2 months after the last infusion of Tagraxofusp.

Who cannot join

  • The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB M3).
  • The patient has persistent clinically significant toxicities Grade ≥ 2 from previous chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests (as mandated in the inclusion criteria)).
  • 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.
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  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Ohio State University

    Columbus, Ohio, 43210

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27705

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Columbia University Medical Center

    New York, New York, 10032

  • University of Pittsburgh Medical Center Presbyterian Shady Side

    Pittsburgh, Pennsylvania, 15213

  • H. Lee Moffiitt Cancer Center & Research Institute

    Tampa, Florida, 12902

Other trials in United States

About this study

Official title: Tagraxofusp in Patients With Acute Myeloid Leukemia (AML) and Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

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.

Read the detailed description

Study 0114 is a multi-stage, non-randomized, open-label, multicenter study of Tagraxofusp in First line and Relapsed/Refractory (R/R) Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) and Acute Myeloid Leukemia (AML) patients divided into 4 stages.

Each study stage has its own unique objectives and patient population, with Stage 1 representing the dose escalation phase and Stage 3 the pivotal phase.

In Stages 1 and 2, both patients with BPDCN (first-line and R/R) and AML were enrolled; Stage 3 enrolled previously untreated (first-line) BPDCN patients only. A separate stage, Stage 4, enrolled First-line and R/R BPDCN patients to further characterize safety and efficacy of Tagraxofusp.

The primary study objectives are reported below by stage:

Stage 1: to determine the Maximum Tolerated Dose (MTD) (or Maximum Tested Dose, MTeD where multiple DLTs were not observed) of Tagraxofusp administered at the following dose levels 7, 9, 12, 16 µg/kg/day

Stage 2: cohort expansion to determine the efficacy and safety of Tagraxofusp at the MTD selected in Stage 1

Stage 3 (pivotal): to determine the efficacy and safety of Tagraxofusp in patients with First-line BPDCN

Stage 4: to further characterize the efficacy and safety of Tagraxofusp in patients with both First-line and R/R BPDCN

Being tested
Tagraxofusp
Medical subject headings
Blastic Plasmacytoid Dendritic Cell Neoplasm, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TagraxofuspDrug

    Also called SL-401

Study groups in NCT02113982
Study groupRoleWhat they receive
First-Line Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)ExperimentalIntervention: Tagraxofusp
Receives: Drug: Tagraxofusp
Relapse/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)ExperimentalIntervention: Tagraxofusp
Receives: Drug: Tagraxofusp
Acute Myeloid LeukemiaExperimentalIntervention: Tagraxofusp
Receives: Drug: Tagraxofusp

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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)

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

Secondary outcomes (5)

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

    CR rate, defined as the percentage of patients who achieved CR+ CR 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)

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

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

    Duration of complete response (CR) defined as the time from when the criteria are first met for CR+CRc (whichever was recorded first) until the date that the criteria for relapse after CR+CRc are met, according to the previously reported criteria for CR and CRc and following criteria of relapse after CR+CRc (Cheson BD et al. J Clin Oncol 2007;25:579-586.):

    Marrow: blast percentage >5% (if no peripheral blasts, then confirmation aspirate required ≥ 1week later)

    Peripheral blood: presence of leukemic blasts

    Skin: increase in skin score greater than the sum of nadir plus 50% baseline score

    Nodal masses: appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase from nadir in SPD of more than one node, or ≥50% increase from nadir in longest diameter of a previously identified node >1cm in short axis

    Spleen, liver: >50% increase from nadir in the SPD of any previous lesions

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

  3. ORR in First-line BPDCN, R/R BPDCN and AML

    Objective response rate (ORR) defines as the percentage of patients who achieved CR (CR+CRc), CR with incomplete blood count recovery (CRi), or partial response (PR) after treatment with Tagraxofusp according to the previously reported definitions of CR, CRc and the following one of CRi and PR:

    CRi: CR with incomplete of neutrophil and/or platelet count and absence of leukemic blast in the peripheral blood

    Marrow: PR defined as decrease by ≥50% in blast percentage to 5-25%

    Peripheral blood: PR defined as normalization of neutrophil count (≥ 1,000/µL) and platelet count (≥ 100,000/µL)

    Skin: 50%-<100% clearance of all skis lesions from baseline; no new lesions in patients without lesions at baseline

    Nodal masses: ≥50% decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes

    Spleen, liver: ≥50% in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen

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

  4. OS in First-line BPDCN, R/R BPDCN and AML

    Overall survival (months) defined as the time from the date of first infusion of Tagraxofusp to the date of death from any cause

    Measured: 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

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

    Bridge to Stem Cell Transplant (SCT) defined as the percentage of patients who received SCT subsequent to achieving an Investigator-determined outcome from Tagraxofusp that was deemed by the Investigator to enable an SCT

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2014 (estimated)
  2. Study startSep 2014
  3. Primary completion1 Feb 2020
  4. Study completion12 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
138 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02113982
Sponsor's protocol ID
STML-401-0114
Status last verified
Jul 2024
First submitted
13 Mar 2014
Last updated
1 Aug 2024
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 41486505

  • 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.

    PubMed 35820082

  • 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.

    PubMed 31018069

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tagraxofusp in people with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) and Acute Myeloid Leukemia (AML), run by Stemline Therapeutics, Inc. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD (Stage 1) (time frame: 21-day period after the first dose (cycle 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02113982, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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