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

NCT02268253 | Completed Phase 1 Results DMC

• 1 other identifier: STML-401-0314
• Study Type: interventional
• Target: 82
• Locations: 2 countries
• Sites: 24

Brief 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. 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).

Conditions

Myelofibrosis; Chronic Myelomonocytic Leukemia

Keywords

MF; CMML; CMML-1; CMML-2

Outcome Measures

Primary Outcomes (2)

• 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.

  21 days of Cycle 1 (21 days/cycle)

• 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.

  1145 days

Study Arms (6)

Dose Level 1 - Tagraxofusp - 7 micrograms/kilogram (µg/kg)/day - Chronic Myelomonocytic Leukemia

EXPERIMENTAL

Drug: Tagraxofusp Injection

Dose Level 2 - Tagraxofusp - 9 µg/kg/day - Chronic Myelomonocytic Leukemia

EXPERIMENTAL

Drug: Tagraxofusp Injection

Dose Level 3 - Tagraxofusp - 12 µg/kg/day - Chronic Myelomonocytic Leukemia

EXPERIMENTAL

Drug: Tagraxofusp Injection

Dose Level 1 - Tagraxofusp - 7 µg/kg/day - Myelofibrosis

EXPERIMENTAL

Drug: Tagraxofusp Injection

Dose Level 2 - Tagraxofusp - 9 µg/kg/day - Myelofibrosis

EXPERIMENTAL

Drug: Tagraxofusp Injection

Dose Level 3 - Tagraxofusp - 12 µg/kg/day - Myelofibrosis

EXPERIMENTAL

Drug: Tagraxofusp Injection

Interventions

Tagraxofusp Injection DRUG

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

Also known as: SL-401, Elzonris

Dose Level 1 - Tagraxofusp - 7 micrograms/kilogram (µg/kg)/day - Chronic Myelomonocytic Leukemia; Dose Level 1 - Tagraxofusp - 7 µg/kg/day - Myelofibrosis; Dose Level 2 - Tagraxofusp - 9 µg/kg/day - Chronic Myelomonocytic Leukemia; Dose Level 2 - Tagraxofusp - 9 µg/kg/day - Myelofibrosis; Dose Level 3 - Tagraxofusp - 12 µg/kg/day - Chronic Myelomonocytic Leukemia; Dose Level 3 - Tagraxofusp - 12 µg/kg/day - Myelofibrosis

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Stemline Therapeutics, Inc.: lead

Study Sites (24)

University of California, San Francisco

Clovis, California, 93611, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana Blood and Bone Marrow Transplantation

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

• 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.

  PMID: 41146971 DERIVED

• 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.

  PMID: 40919483 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis; Leukemia, Myelomonocytic, Chronic

Interventions

tagraxofusp

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

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

clinicaltrials@menarinistemline.com

1-877-332-7967

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 10, 2014
• First Posted: October 20, 2014
• Study Start: February 10, 2016
• Primary Completion: March 27, 2023
• Study Completion: March 27, 2023
• Last Updated: January 6, 2025
• Results First Posted: January 6, 2025

Record last verified: 2024-12

Locations

CA (2); US (22)