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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.

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).

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 : December 2020
Estimated Study Completion Date : December 2021


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

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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

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.


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: January 18, 2020
Last Verified: January 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