SL-401 in Advanced, High Risk Myeloproliferative Neoplasms (Systemic Mastocytosis, Advanced Symptomatic Hypereosinoophic Disorder, Myelofibrosis, Chronic Myelomonocytic Leukemia)

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. Identifier: NCT02268253
Recruitment Status : Recruiting
First Posted : October 20, 2014
Last Update Posted : January 29, 2018
Information provided by (Responsible Party):
Stemline Therapeutics, Inc.

Brief Summary:
This is a non-randomized open label multi-center study. Patients with high-risk myeloproliferative neoplasms (systemic mastocytosis [SM], advanced symptomatic hypereosinoophic disorder [PED], myelofibrosis [MF], and chronic myelomonocytic leukemia [CMML]) will be treated with SL-401, which will be administered as a brief intravenous infusion for 3 consecutive days initially every 21 days for 4 cycles; every 28 days for cycles 5-7; then every 42 days. Stage 1 will consist of a period in which several doses of SL-401 are evaluated. The Stage 2 portion will enroll up to 18 patients with each of the 2 myeloproliferative malignancies: MF and CMML. In entirety, the Stage 2 portion will consist of up to 36 patients who will be treated at a maximum tolerated dose or maximum tested dose in which multiple dose-limiting toxicities are not observed (identified in Stage 1).

Condition or disease Intervention/treatment Phase
Myelofibrosis Chronic Myelomonocytic Leukemia Drug: SL-401 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: SL-401 in Patients With Advanced, High Risk Myeloproliferative Neoplasms (Systemic Mastocytosis, Advanced Symptomatic Hypereosinoophic Disorder, Myelofibrosis, Chronic Myelomonocytic Leukemia)
Study Start Date : December 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: Completed first cycle of therapy and for an expected 24 weeks ]
    Participants will be followed for the duration of the study, an expected 24 weeks

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

Inclusion Criteria:

All Patients (Stages 1 and 2):

  1. The patient is ≥18 years old
  2. The patient has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
  3. 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 or 2-dimensional (2-D) echocardiogram 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 (or ≤114 µmol/L)
    • 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 (or ≤26 µmol/L)
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN)
    • CPK ≤2.5 times the ULN
  4. If a woman of child bearing potential, the patient has a negative serum or urine pregnancy test within 1 week prior to SL-401 treatment (intervals shorter than 1 week are acceptable, if required by institutional guidelines)
  5. The patient has signed informed consent prior to initiation of any study-specific procedures or treatment
  6. The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for response assessments
  7. The patient agrees to use acceptable contraceptive methods for the duration of time in the study, and to continue to use acceptable contraceptive methods for 2 months after the last SL-401 infusion
  8. Patient has an absolute neutrophil count (ANC) ≥0.5×10⁹/L

Additional Inclusion Criteria Specific to Patients with MF and CMML (Stages 1 and 2)

Exclusion Criteria:

All Patients (Stages 1 and 2):

  1. Patient has persistent clinically significant toxicities Grade ≥2 from previous chemotherapy not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
  2. Patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry
  3. Patient has received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent.
  4. Patient has previously received treatment with SL-401 or has a known hypersensitivity to any components of the drug product
  5. 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
  6. 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 or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
  7. 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
  8. 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
  9. 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
  10. 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
  11. Patient is pregnant or breast feeding
  12. Patient has known human immunodeficiency virus (HIV)
  13. Patient has evidence of active or chronic Hepatitis B or Hepatitis C infection.
  14. Patient is oxygen-dependent
  15. Patient has any medical condition that in the Investigator's opinion place the patient at an unacceptably high risk for toxicities

Additional Exclusion Criteria Specific to Patients with MF and CMML (Stages 1 and 2)

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 identifier (NCT number): NCT02268253

Contact: Shay Shemesh, MS 646-502-2309

United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Haris Ali, M.D.    626-256-4673 ext 62684   
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   
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   
Principal Investigator: Abdulraheem Yacoub, M.D.         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Moshe Talpaz, MD   
Principal Investigator: Moshe Talpaz, M.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mrinal Patnaik, M.B.B.S..   
Principal Investigator: Mrinal Patnaik, M.B.B.S.         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: James McCloskey, M.D.   
Principal Investigator: James McCloskey, M.D.         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Eunice Wang, MD    716-845-3544   
Principal Investigator: Eunice Wang, MD         
Weill Cornell Medical Center Recruiting
New York, New York, United States, 10021
Contact: Sangman Lee, M.D.   
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   
Principal Investigator: Naveen Pemmaraju, M.D.         
Canada, Alberta
University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2G3
Contact: Minakshi Taparia, MD    780-407-1584      
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   
Principal Investigator: Vikas Gupta, M.D.         
Sponsors and Collaborators
Stemline Therapeutics, Inc.

Responsible Party: Stemline Therapeutics, Inc. Identifier: NCT02268253     History of Changes
Other Study ID Numbers: STML-401-0314
First Posted: October 20, 2014    Key Record Dates
Last Update Posted: January 29, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Primary Myelofibrosis
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myeloproliferative Disorders
Mastocytosis, Systemic
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases