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Tagraxofusp (SL-401) in Patients With CMML or MF

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ClinicalTrials.gov Identifier: NCT02268253
Recruitment Status : Recruiting
First Posted : October 20, 2014
Last Update Posted : August 9, 2021
Sponsor:
Information provided by (Responsible Party):
Stemline Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE October 10, 2014
First Posted Date  ICMJE October 20, 2014
Last Update Posted Date August 9, 2021
Actual Study Start Date  ICMJE December 2014
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
  • Rate and severity of treatment-emergent adverse events [ Time Frame: Through 30 days post last dose of tagraxofusp ]
    Characterize the safety profile of tagraxofusp in patients with CMML and MF by assessing rates of adverse events
  • Evaluation of rate of response [ Time Frame: Through 12 months post last dose of tagraxofusp ]
    Evaluate the efficacy of tagraxofusp as measured by the rate (%) of response
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2014)
Maximum Tolerated Dose [ Time Frame: Completed first cycle of therapy, an expected 24 weeks ]
Participants will be followed for the duration of the study, an expected 24 weeks
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tagraxofusp (SL-401) in Patients With CMML or MF
Official Title  ICMJE Tagraxofusp (SL-401) in Patients With Chronic Myelomonocytic Leukemia (CMML) or Myelofibrosis (MF). [Prior Title: SL-401 in Patients With Advanced, High Risk Myeloproliferative Neoplasms (Systemic Mastocytosis, Advanced Symptomatic Primary Eosinophilic Disorder, Myelofibrosis, Chronic Myelomonocytic Leukemia).]
Brief Summary This multi-center, multi-arm trial is evaluating the safety and efficacy of tagraxofusp, a CD123-targeted therapy, in patients with either chronic myelomonocytic leukemia (CMML) or myelofibrosis (MF). There are two CMML cohorts, one enrolling patients with CMML (CMML-1 or CMML-2) who are refractory/resistant or intolerant to hypomethylating agents (HMA), hydroxyurea (HU), or intensive chemotherapy; and one enrolling treatment-naive patients with CMML (CMML-1 or CMML-2) with molecular features associated with poor prognosis. The MF cohort will enroll patients who are resistant/refractory or intolerant to approved JAK therapy (JAK1/JAK2 or JAK2).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelofibrosis
  • Chronic Myelomonocytic Leukemia
Intervention  ICMJE Drug: SL-401
Other Name: tagraxofusp-erzs
Study Arms  ICMJE Experimental: Tagraxofusp (SL-401)
Intervention: Drug: SL-401
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 17, 2019)
130
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2014)
100
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Abbreviated Inclusion Criteria:

All Patients (Stages 2 and 3A):

  1. The patient is ≥18 years old.
  2. The patient has a life expectancy of >6 months.
  3. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
  4. 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 multigated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
    • Serum creatinine ≤1.5 mg/dL
    • Serum albumin ≥3.2 g/dL (or ≥32 g/L) in the absence of receipt of (IV) albumin within the previous 72 hours
    • Bilirubin ≤1.5 mg/dL
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN)
    • Creatine phosphokinase (CPK) ≤2.5 times the ULN
    • Absolute neutrophil count (ANC) ≥0.5 × 10⁹/L

Additional Abbreviated Inclusion Criteria Specific to Patients with MF (Stage 2):

  1. Patient meets the 2016 WHO diagnostic criteria for MF and has an IPSS/DIPSS/DIPSS-plus intermediate-2 or high-risk disease. Patients with IPSS/DIPSS/DIPSS-plus low or intermediate-1 risk disease who have at least one of the following symptoms are also eligible: MF-related anemia (Hb <10 g/dL), splenomegaly (palpable size >10 cm), leukocytosis (WBC >25 × 10⁹/L), marked thrombocytosis (platelet count >1000 × 10⁹/L), or constitutional symptoms (weight loss >10%, during prior 6 months or fever [>37.5ºC or drenching night sweats for >6 weeks]), as recommended by the ELN/IWG 2018 criteria.
  2. Patient is 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.
  3. Patient is not eligible for an immediate allo-SCT.

Additional Abbreviated Inclusion Criteria Specific to Patients with CMML (Stage 3A):

  1. Patient has a 2016 WHO-defined diagnosis of CMML (persistent monocytosis ≥1 × 10⁹/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 CML, ET, PV, and acute promyelocytic leukemia; if eosinophilic, neither PDGFRA, PDGFRB, FGFR1 rearrangements nor PCM1-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).
  2. Patient has 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).
  3. Patient is refractory/resistant/intolerant to HMAs, or HU, or intensive chemotherapy OR patient is 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 GFM, MMM, and the CMML specific prognostic model (CPSS-Mol), and thus is not expected to benefit from HMAs.
  4. Patient is ineligible for an immediate allo-SCT.

Abbreviated Exclusion Criteria:

All Patients (Stages 2 and 3A):

  1. Persistent clinically significant toxicities Grade ≥2 from previous therapies not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
  2. Treatment with any disease-related therapy, including radiation therapy or investigational agent, within 14 days of study entry.
  3. Allogeneic SCT within 3 months of study entry.
  4. Previous treatment with tagraxofusp or known hypersensitivity to any components of the drug product.
  5. Active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that can confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) and/or ongoing active malignancy or substantial potential for recurrence must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of progressive disease.
  6. Clinically significant cardiovascular disease, pulmonary disease, or known active or suspected disease involvement of the central nervous system (CNS).
  7. Receiving immunosuppressive therapy, with the exception of corticosteroids as specified in the inclusion criteria and tacrolimus, for treatment or prophylaxis of graft-versus-host disease (GVHD).
  8. Uncontrolled intercurrent illness.
  9. Patient is pregnant or breast feeding.
  10. Patient has known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C.
  11. Patient is oxygen-dependent.

Additional Exclusion Criteria Specific to Patients with MF and CMML (Stages 2 and 3A) apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stemline Trials Trials@stemline.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02268253
Other Study ID Numbers  ICMJE STML-401-0314
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Stemline Therapeutics, Inc.
Study Sponsor  ICMJE Stemline Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Stemline Therapeutics, Inc.
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP