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MyelofibrosisPhase 1/2NCT02268253

Tagraxofusp (SL-401) in Participants With Chronic Myelomonocytic Leukemia (CMML) and Myelofibrosis (MF)

A Phase 1/2 study testing Tagraxofusp Injection in people with Myelofibrosis and Chronic Myelomonocytic Leukemia, run by Stemline Therapeutics, Inc. at 24 sites in 2 countries.

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 multicenter, multi-arm trial evaluated the safety and efficacy of tagraxofusp, a cell division cycle protein 123 homolog-targeted therapy, in participants with either CMML or MF. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tagraxofusp Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
24 sitesin 2 countries
Study dates
10 Feb 2016to 27 Mar 2023
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

  • All Participants - Participants meeting all the following criteria were considered for enrollment:
  • The participant had a life expectancy of > 6 months.
  • The participant had an Eastern Cooperative Oncology Group performance status of 0-2.
  • The participant had adequate baseline organ function, including cardiac, renal, and hepatic function:
  • Left ventricular ejection fraction 2: institutional lower limit of normal as measured by multigated acquisition scan or 2-dimensional echocardiogram within 28 days prior to the start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram.
  • Serum creatinine ≤ 1.5 milligrams/deciliter (dL).
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  • Serum albumin ≥ 3.2 grams (g)/dL (or 32 g/liter [L]) in the absence of receipt of intravenous albumin within the previous 72 hours.
  • Aspartate transaminase and alanine transaminase ≤ 2.5 times the upper limit of normal (ULN).
  • Creatine phosphokinase ≤ 2.5 times the ULN.
  • Absolute neutrophil count ≥ 0.5×10^9/L.
  • If a woman of child-bearing potential, the participant had a negative serum or urine pregnancy test within 1 week prior to tagraxofusp treatment (intervals shorter than 1 week are acceptable, if required by institutional guidelines).
  • The participant (either male or female) agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 1 week after the last tagraxofusp infusion.
  • The participant can adhere to the study visit schedule and other protocol requirements, including follow-up for response assessments.
  • Myelofibrosis (Stage 2) - Participants with MF meeting all of the following criteria, in addition to those specified for all participants, above, are eligible for enrollment in Stage 2:
  • Participant meets the 2016 World Health Organization (WHO) diagnostic criteria for MF and has an International Prognostic Scoring System/Dynamic International Prognostic Scoring System (IPSS/DIPSS)/DIPSS-plus intermediate-2 or high-risk disease. Participants with IPSS/DIPSS/DIPSS-plus low or intermediate-1 risk disease who have at least 1 of the following symptoms are also eligible: MF-related anemia (hemoglobin < 10 g/dL), splenomegaly (palpable size > 10 centimeters), leukocytosis (white blood cell count [WBC] > 25×10^9/L), marked thrombocytosis (platelet count > 1,000×10^9/L), or constitutional symptoms (weight loss > 10%, during prior 6 months or fever [> 37.5 degrees Celsius or drenching night sweats for > 6 weeks]), as recommended by the European LeukemiaNet/International Working Group (ELN/IWG) 2018 criteria.
  • Participant was approved JAK therapy (JAK1/JAK2 or JAK2) resistant/refractory or intolerant, in accordance with the ELN/IWG 2018 criteria, and at least 4 weeks have elapsed between the last dose of any MF-directed drug treatments, excluding HU, and study enrollment (first dose). HU can be continued until 2 weeks prior to study enrollment.
  • Participant was not eligible for an immediate allogeneic-stem cell transplantation.
  • CMML (Stage 3A):
  • Participant had a 2016 WHO-defined diagnosis of CMML (persistent monocytosis ≥ 1×10^9/L for at least 3 months, with other causes excluded, and monocytes ≥10% of WBC in peripheral blood, no criteria and no previous history of CMML, essential thrombocythemia, polycythemia vera, and acute promyelocytic leukemia; if eosinophilic, neither platelet-derived growth factor receptor A, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1 rearrangements nor pericentriolar material 1-JAK2 translocation; < 20% blasts in peripheral blood and bone marrow aspirate; > 1 following criteria: dysplasia in > 1 myeloid lineage, acquired clonal cytogenetic or molecular abnormality in hematopoietic cells).
  • Participant had 2016 WHO-defined CMML-1 (2-4% blasts in peripheral blood and/or 5-9% blasts in bone marrow) and CMML-2 (5-19% blasts in peripheral blood and/or 10-19% blasts in bone marrow, and/or presence of Auer rods).
  • Participant was refractory/resistant/intolerant, as defined for the purposes of this study (in the absence of a standard definition for CMML) below, to HMAs, HU, or intensive chemotherapy, including:
  • Resistance/intolerance to HU is defined as:
  • Uncontrolled myeloproliferation, (platelets > 400×10^9/L and WBC > 10×10^9/L after 3 months of at least 2 g/day of HU); or
  • Myelosuppression at a clinically relevant dose; or
  • Presence of unacceptable HU-related non-hematological toxicities, such as mucocutaneous manifestations, gastrointestinal symptoms, pneumonitis, or fever at any dose of HU.
  • Conventional definition for HMA failure is defined for the purposes of this study (in the absence of a standard definition for CMML) as:
  • Disease progression following at least 4 to 6 cycles of 5-azacitidine or decitabine; or
  • Relapse after achieving response; or
  • Intolerance to 5-azacitidine or decitabine at the prescribed dose.
  • or
  • Participant was classified as high-risk based on the presence of morphological features, as described by the 2016 WHO prognostic system, and the clinical and molecular features described in molecularly integrated prognostic systems, such as the Groupe Français des Myélodysplasies, Mayo Molecular Model, and the CMML specific prognostic model and thus is not expected to benefit from HMAs.
  • Participant was ineligible for an immediate allogeneic stem cell transplantation (allo-SCT).

Who cannot join

  • Participant had persistent clinically significant toxicities Grade ≥2 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
  • Participant received treatment with any disease-related therapy, including radiation therapy within 14 days of study entry.
  • Participant received an allo-SCT within 3 months of study entry.
  • Participant received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent.
  • Participant previously received treatment with tagraxofusp or has a known hypersensitivity to any components of the drug product.
  • Participant had an active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that could confound the assessment of the study endpoints.
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  • Participant had clinically significant cardiovascular disease (for example, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
  • Participant had uncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would have put the participant at significant risk for pulmonary complications during the study.
  • Participant had known active or suspected disease involvement of the central nervous system (CNS). If suspected due to clinical findings, CNS disease was to be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
  • Note: Other inclusion/exclusion criteria may apply.

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States22 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87106

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Georgia Cancer Center at Augusta University

    Augusta, Georgia, 30912

  • Dana Farber Cancer Institute (DFCI)

    Boston, Massachusetts, 02114

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of California, San Francisco

    Clovis, California, 93611

  • The Ohio State University

    Columbus, Ohio, 43210

  • City of Hope

    Duarte, California, 91010

  • John Theurer Cancer Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana Blood and Bone Marrow Transplantation

    Indianapolis, Indiana, 46237

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • Norton Cancer Institute

    Louisville, Kentucky, 40207

  • Weill Cornell Medical Center

    New York, New York, 10021

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Stanford Cancer Institute

    Stanford, California, 94305

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

Canada2 sites

  • University of Alberta

    Edmonton, Alberta, T6G 2G3

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Tagraxofusp (SL-401) in Patients With Chronic Myelomonocytic Leukemia (CMML)

This multicenter, multi-arm trial evaluated the safety and efficacy of tagraxofusp, a cell division cycle protein 123 homolog-targeted therapy, in participants with either CMML or MF. There were 2 CMML cohorts, 1 enrolled participant with CMML (CMML-1 or CMML-2) who were refractory/resistant or intolerant to hypomethylating agents (HMA), hydroxyurea (HU), or intensive chemotherapy and 1 enrolled treatment-naive participants with CMML (CMML-1 or CMML-2) with molecular features associated with poor prognosis. The MF cohort enrolled participants who were resistant/refractory or intolerant to approved Janus kinase (JAK) therapy (JAK1/JAK2 or JAK2).

Read the detailed description

This was a non-randomized, open-label, multicenter study, divided into 3 stages.

Stage 1: Stage 1 of the study was to enroll participants with CMML, MF, advanced systemic mastocytosis, or advanced symptomatic primary eosinophilic disorder.

Stage 2: Stage 2 was to enroll MF and CMML participants.

Stage 3A: Stage 3A was to enroll 2 populations of participants with CMML, those with CMML-1 or CMML-2 who were refractory/resistant/intolerant to HMAs, HU, or intensive chemotherapy (relapsed/refractory participants); and participants with treatment-naïve CMML-1 or CMML-2 (previously untreated participants) with molecular features associated with a poor prognosis.

Being tested
Tagraxofusp Injection
Keywords
MF, CMML, CMML-1, CMML-2
Medical subject headings
Primary Myelofibrosis, Leukemia, Myelomonocytic, Chronic

What participants receive

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

  • Tagraxofusp InjectionDrug

    Also called SL-401, Elzonris

    Tagraxofusp was administered as a 15-minute intravenous infusion once daily for the first 3 consecutive days of each dosing cycle.

Study groups in NCT02268253
Study groupRoleWhat they receive
Dose Level 1 - Tagraxofusp - 7 micrograms/kilogram (µg/kg)/day - Chronic Myelomonocytic LeukemiaExperimentalNot described
Receives: Drug: Tagraxofusp Injection
Dose Level 2 - Tagraxofusp - 9 µg/kg/day - Chronic Myelomonocytic LeukemiaExperimentalNot described
Receives: Drug: Tagraxofusp Injection
Dose Level 3 - Tagraxofusp - 12 µg/kg/day - Chronic Myelomonocytic LeukemiaExperimentalNot described
Receives: Drug: Tagraxofusp Injection
Dose Level 1 - Tagraxofusp - 7 µg/kg/day - MyelofibrosisExperimentalNot described
Receives: Drug: Tagraxofusp Injection
Dose Level 2 - Tagraxofusp - 9 µg/kg/day - MyelofibrosisExperimentalNot described
Receives: Drug: Tagraxofusp Injection
Dose Level 3 - Tagraxofusp - 12 µg/kg/day - MyelofibrosisExperimentalNot described
Receives: Drug: Tagraxofusp Injection

What is being measured

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

  1. Number of Participants With Dose-limiting Toxicities (DLTs)

    During Stage 1, DLT was defined as any of the following occurring during the first cycle of therapy: any treatment-emergent Grade 4 transaminase or creatine phosphokinase (CPK) elevation (confirmed within 24 hours of initial identification), regardless of duration or relationship to SL-401; any Grade ≥3 non-hematologic toxicity (unrelated to underlying MPN), with the exception of Grade 3 laboratory toxicities that resolve to Grade ≤1 or baseline ≤28 days after the last infusion of SL-401, or the following Grade 3 toxicities if they resolve to Grade ≤1 or baseline ≤21 days after the last infusion of SL-401, arthralgia, myalgia, fever responding to treatment, nausea and/or vomiting (excluding cases that require tube feeding, total parenteral nutrition, or hospitalization) or diarrhea associated with suboptimal prophylaxis or treatment; Grade 4 neutropenia or Grade 4 thrombocytopenia with a duration (at Grade 4) of ≥28 days.

    Measured: 21 days of Cycle 1 (21 days/cycle)

  2. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants (responders) who achieved disease-specific complete response (CR) or partial response (PR) after treatment. For response assessment of myelofibrosis during both Stage 1 and Stage 2, the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet (IWG-MRT/ELN 2013) criteria were used. For chronic myelomonocytic leukemia, during both Stage 1 and Stage 2, the International Working Group 2006 response criteria for myelodysplastic syndromes (IWG MDS 2006) were used for response assessment while the Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) 2015 criteria were used for response assessment during Stage 3A.

    Measured: 1145 days

Timeline

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

  1. First posted20 Oct 2014 (estimated)
  2. Study start10 Feb 2016
  3. Primary completion27 Mar 2023
  4. Study completion27 Mar 2023

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
Sequential
Masking
None (open label)
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02268253
Sponsor's protocol ID
STML-401-0314
Status last verified
Dec 2024
First submitted
10 Oct 2014
Last updated
6 Jan 2025
Data monitoring committee
Yes

Publications

  • Yacoub A, Ali H, Gupta V, Wang ES, Patnaik MM, Schiller GJ, Taparia M, Mughal TI, Lindsay R, Galleu A, Gupta I, Pemmaraju N. Final safety and efficacy results from a phase 1/2 study of tagraxofusp, a CD123-targeted therapy, for myelofibrosis. Blood Neoplasia. 2025 Aug 25;2(4):100165. doi: 10.1016/j.bneo.2025.100165. eCollection 2025 Nov.

    PubMed 41146971

  • Patnaik MM, Ali H, Wang ES, Yacoub A, Foran JM, Gupta V, Schiller GJ, Stevens DA, Talpaz M, Wall S, Lasho TL, Mangaonkar AA, Badar T, Lindsay R, Galleu A, Gupta I, Pemmaraju N, Garcia-Manero G. Tagraxofusp, a CD123-targeted therapy, for chronic myelomonocytic leukemia: final results of a phase 1/2 study. Blood Neoplasia. 2025 May 11;2(4):100115. doi: 10.1016/j.bneo.2025.100115. eCollection 2025 Nov.

    PubMed 40919483

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tagraxofusp Injection in people with Myelofibrosis and Chronic Myelomonocytic Leukemia, run by Stemline Therapeutics, Inc. at 24 sites in 2 countries.

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 32 inclusion and 10 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 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Canada. 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 6 Jan 2025). 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?

Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: 21 days of Cycle 1 (21 days/cycle)). 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 NCT02268253, which also lists 2 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 6 Jan 2025.

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