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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 : January 18, 2020
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 January 18, 2020
Actual Study Start Date  ICMJE December 2014
Estimated Primary Completion Date December 2020   (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 is a non-randomized, open-label, multicenter study, divided into multiple stages. Patients with chronic myelomonocytic leukemia (CMML) or myelofibrosis (MF) will be treated with tagraxofusp (SL-401), which will be administered as a brief intravenous infusion for 3 consecutive days every 21 days during Cycles 1-4; and every 28 days during Cycle 5 and beyond. Stage 1 consisted of a period in which several doses of SL-401 were evaluated; Stage 1 is now closed. The Stage 2 portion will enroll up to 30 patients with CMML and up to 50-55 patients with MF, who will be treated at the maximum tested dose in which multiple dose-limiting toxicities were not observed (identified in Stage 1). Stage 3A will enroll 2 populations of patients with CMML, those with CMML-1 or CMML-2 who are refractory/resistant/intolerant to HMAs, or HU, or intensive chemotherapy; and treatment-naive patients with CMML-1 or CMML-2 with molecular features associated with a poor prognosis (up to 20 patients each).
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 December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  5. If a woman of child bearing potential (WOCBP), the patient has 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).
  6. The patient (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.
  7. The patient has signed informed consent prior to initiation of any study-specific procedures or treatment.
  8. The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for response assessments.

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 MF-related anemia (Hb <10 g/dL), splenomegaly (palpable size >10 cm), leukocytosis (WBC >25 × 10⁹/L), marked thrombocytosis (platelet count >100 × 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, are also eligible.
  2. Patient is JAK (JAK1/JAK2 or JAK2) therapy resistant/refractory or intolerant, in accordance with the ELN/IWG 2018 criteria, and at least 2 weeks have elapsed between the last dose of any MF-directed drug treatments (including investigational therapies but excluding HU) and 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 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.
  5. If patient has splenomegaly present by palpation, spleen volume must be determined by MRI/CT at baseline.
  6. Patient must have a baseline bone marrow biopsy/aspirate with cytogenetics.

Exclusion Criteria:

All Patients (Stages 2 and 3A):

  1. Patient has persistent clinically significant toxicities Grade ≥2 from previous therapies, including chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
  2. Patient has received treatment with any disease-related therapy, including radiation therapy within 14 days of study entry.
  3. Patient has received an allo-SCT within 3 months of study entry.
  4. Patient has received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent.
  5. Patient has previously received treatment with tagraxofusp or has a known hypersensitivity to any components of the drug product.
  6. Patient has an 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.
  7. Patient has clinically significant cardiovascular disease (e.g., 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 of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
  8. Patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study.
  9. Patient has known active or suspected disease involvement of the central nervous system (CNS). If suspected due to clinical findings, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
  10. Patient is 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). 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 drug and there must be no evidence of Grade ≥2 GVHD.
  11. Patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness that would limit compliance with study requirements.
  12. Patient is pregnant or breast feeding.
  13. Patient has known human immunodeficiency virus (HIV).
  14. Patient has evidence of active or chronic Hepatitis B or Hepatitis C infection.
  15. Patient is oxygen-dependent.
  16. Patient has any medical condition that in the Investigator's opinion places the patient at an unacceptably high risk for toxicities.

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 January 2020

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