Clinical Trials /

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

NCT02268253

Description:

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).

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tagraxofusp (SL-401) in Patients With CMML or MF
  • Official Title: 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).]

Clinical Trial IDs

  • ORG STUDY ID: STML-401-0314
  • NCT ID: NCT02268253

Conditions

  • Myelofibrosis
  • Chronic Myelomonocytic Leukemia

Interventions

DrugSynonymsArms
SL-401tagraxofusp-erzsTagraxofusp (SL-401)

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Tagraxofusp (SL-401)Experimental
  • SL-401

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate and severity of treatment-emergent adverse events
Time Frame:Through 30 days post last dose of tagraxofusp
Safety Issue:
Description:Characterize the safety profile of tagraxofusp in patients with CMML and MF by assessing rates of adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Stemline Therapeutics, Inc.

Trial Keywords

  • MF
  • CMML
  • CMML-1
  • CMML-2

Last Updated

January 14, 2020