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).
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).]
Myelofibrosis Chronic Myelomonocytic Leukemia MF CMML CMML-1 CMML-2 Leukemia Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Primary Myelofibrosis Tagraxofusp (SL-401)
For people ages 18 years and up
Abbreviated Inclusion Criteria:
All Patients (Stages 2 and 3A):
- The patient is ≥18 years old.
- The patient has a life expectancy of >6 months.
- The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
- 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):
- 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.
- 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.
- Patient is not eligible for an immediate allo-SCT.
Additional Abbreviated Inclusion Criteria Specific to Patients with CMML (Stage 3A):
- 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).
- 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).
- 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.
- Patient is ineligible for an immediate allo-SCT.
Abbreviated Exclusion Criteria:
All Patients (Stages 2 and 3A):
- Persistent clinically significant toxicities Grade ≥2 from previous therapies not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
- Treatment with any disease-related therapy, including radiation therapy or investigational agent, within 14 days of study entry.
- Allogeneic SCT within 3 months of study entry.
- Previous treatment with tagraxofusp or known hypersensitivity to any components of the drug product.
- 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.
- Clinically significant cardiovascular disease, pulmonary disease, or known active or suspected disease involvement of the central nervous system (CNS).
- 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).
- Uncontrolled intercurrent illness.
- Patient is pregnant or breast feeding.
- . Patient has known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C.
- . Patient is oxygen-dependent.
Additional Exclusion Criteria Specific to Patients with MF and CMML (Stages 2 and 3A) apply.
- University of California, Los Angeles
accepting new patients
Los Angeles California 90095 United States
- City of Hope
accepting new patients
Duarte California 91010 United States
Lead Scientist at UC Health
- Gary Schiller, M.D. (ucla)
Professor-in-Residence, Medicine. Authored (or co-authored) 74 research publications.
- accepting new patients
- Start Date
- Completion Date
- Stemline Therapeutics, Inc.
- Phase 2
- Study Type
- Last Updated