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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02268253
Recruitment Status : Recruiting
First Posted : October 20, 2014
Last Update Posted : June 4, 2020
Sponsor:
Information provided by (Responsible Party):
Stemline Therapeutics, Inc.

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).

Condition or disease Intervention/treatment Phase
Myelofibrosis Chronic Myelomonocytic Leukemia Drug: SL-401 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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).]
Actual Study Start Date : December 2014
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022


Arm Intervention/treatment
Experimental: Tagraxofusp (SL-401) Drug: SL-401
Other Name: tagraxofusp-erzs




Primary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02268253


Contacts
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Contact: Stemline Trials Trials@stemline.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Haris Ali, M.D.    626-256-4673 ext 62684    harisali@coh.org   
Principal Investigator: Haris Ali, M.D.         
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Gary Schiller, MD    310-825-5513    gschiller@mednet.ucla.edu   
Principal Investigator: Gary Schiller, M.D.         
United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Abdulraheem Yacoub, M.D.    913-588-6029    ayacoub@kumcc.edu   
Principal Investigator: Abdulraheem Yacoub, M.D.         
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
Contact: Don A Stevens, MD       Don.Stevens@nortonhealthcare.org   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mrinal Patnaik, M.B.B.S..    424-208-8866    patnaik.mrinal@mayo.edu   
Principal Investigator: Mrinal Patnaik, M.B.B.S.         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Eunice Wang, MD    716-845-3544    eunice.wang@roswellpark.org   
Principal Investigator: Eunice Wang, MD         
Weill Cornell Medical Center Recruiting
New York, New York, United States, 10021
Contact: Sangman Lee, M.D.    646-962-2700    sal9053@med.cornell.edu   
Principal Investigator: Sangman Lee, M.D.         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Naveen Pemmaraju, M.D.    713-792-4956    npemmaraju@mdanderson.org   
Principal Investigator: Naveen Pemmaraju, M.D.         
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2G3
Contact: Minakshi Taparia, MD    780-407-6090    mtaparia@ualberta.ca   
Principal Investigator: Minakshi Taparia, M.D.         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Vikas Gupta, MD    416-946-4521    vikas.gupta@uhn.ca   
Principal Investigator: Vikas Gupta, M.D.         
Sponsors and Collaborators
Stemline Therapeutics, Inc.
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Responsible Party: Stemline Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02268253    
Other Study ID Numbers: STML-401-0314
First Posted: October 20, 2014    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020
Keywords provided by Stemline Therapeutics, Inc.:
MF
CMML
CMML-1
CMML-2
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Primary Myelofibrosis
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases