SL-401 in Combination With Azacitidine in Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

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: NCT03113643
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : January 17, 2018
Stemline Therapeutics, Inc.
Information provided by (Responsible Party):
Andrew Lane, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying a drug as a possible treatment for diagnosis of AML and high-risk MDS.

The interventions involved in this study are:

  • SL-401
  • Azacitidine

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Drug: Azacitidine Drug: SL-401 Phase 1

Detailed Description:

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has approved Azacitidine as a treatment option for this disease. SL-401 is an investigational drug, which means it is not approved by the FDA as a treatment for any disease.

In this research study, the study drug SL-401 will be combined with the standard dose of azacitidine. The goal of this research study is to try and determine the safest, highest dose of study drug, SL-401, in combination with azacitidine that can be given to patients with AML or high-risk MDS. SL-401 works by stopping or slowing the growth of cancer stem cells, which are the undeveloped cells which can develop into cancer cells. The goals of this research study are to look at if this combination works to help treat cancer and if there is any lasting effect of this combination . This study will also look at how the SL-401, in combination with azacitidine, affects certain proteins in the blood and bone marrow. SL-401 has been given to patients with AML and MDS in the past, but this is the first time it will be given in combination with another drug.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of SL-401 in Combination With Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia (AML) or in Treatment-Naive AML Not Eligible for Standard Therapy or in Subjects With High-Risk Myelodysplastic Syndrome (MDS)
Actual Study Start Date : June 26, 2017
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2023

Arm Intervention/treatment
Experimental: SL-401+ Azacitidine
SL-401 will be administered every 4 weeks, on a 28 day cycle; SL-401 will be given intravenously; Azacitidine will be administered every 4 weeks, on a 28 day cycle; Azacitidine will be given intravenously or subcutaneously
Drug: Azacitidine
Other Name: Vidaza

Drug: SL-401
SL-401 works by targeting leukemia cells (blasts), and also possibly by stopping or slowing the growth of cancer stem cells, which are the undeveloped cells which can develop into cancer cells.

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Complete Response Rate [ Time Frame: 2 years ]
  2. Time to response and duration of response [ Time Frame: 2 years ]
  3. Progression Free Survival [ Time Frame: 2 years ]
  4. Overall Survival [ Time Frame: 2 years ]

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

Inclusion Criteria:

  • Histologically confirmed diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) per 2016 WHO criteria
  • CD123 / IL3RA expression on the subject's AML, determined locally within 3 months of first protocol treatment
  • Age >= 18 years with relapsed or refractory AML (hydroxyurea is not considered a prior treatment regimen)


--Age >= 18 years with treatment-naïve AML who decline intensive induction chemotherapy or who are unfit due to co-morbidity or other factor (hydroxyurea is not considered a prior treatment regimen)


  • Age > 18 years with MDS and >= 10% myeloblasts in the bone marrow

    • ECOG performance status 0, 1, or 2
    • Adequate organ function as defined by:
  • Albumin > 3.2 g/dL (in the absence of receipt of intravenous albumin in the previous 72 hours)
  • Serum creatinine < 1.5x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN
  • Total bilirubin < 2x ULN (if thought to be > 2x ULN due to Gilbert's disease or the patient's AML, must discuss with the PI)
  • Creatine phosphokinase (CPK) < 2.5x ULN
  • Left ventricular ejection fraction > institutional lower limit of normal by MUGA scan or echocardiogram within 30 days of first protocol treatment

    • Ability to understand and the willingness to sign a written informed consent document.
    • Able to adhere to study visit schedule and other protocol requirements including follow-up for survival assessment
    • Women of child-bearing potential must agree to use adequate contraception for the duration of study participation and for 2 months after completion of SL-401 and azacitidine administration. Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation and 2 months after completion of SL-401 and azacitidine administration.

Exclusion Criteria:

  • Prior treatment with a hypomethylating agent (including but not limited to azacitidine or decitabine)
  • Prior treatment with SL-401
  • Diagnosis of acute promyelocytic leukemia
  • Received treatment with chemotherapy, radiation, or biologic cancer therapy within 14 days of first protocol treatment. Prior and concurrent hydroxyurea is permitted.
  • Hematopoietic stem cell transplantation (HSCT) within 60 days of screening, or receipt of immunosuppressive therapy for graft-versus-host disease treatment or prophylaxis within 30 days of screening, or active graft-versus-host-disease
  • Known CNS involvement by AML
  • Known positive status for HIV infection; known active hepatitis B or hepatitis C infection
  • Clinically significant cardiopulmonary disease including uncontrolled or NYHA class 3 or 4 congestive heart failure, uncontrolled angina, uncontrolled hypertension, uncontrolled arrhythmia, myocardial infarction or stroke within 6 months of first protocol treatment, or QTc > 480 ms
  • Patients with known active advanced malignant solid tumors are excluded (except for basal or squamous skin cancers, or carcinomas in situ). Patients with additional hematologic malignancies that require treatment are excluded.
  • Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in the developing fetus with SL-401 and azacitidine (negative urine or serum pregnancy test required within 14 days of Cycle 1, Day 1). Because nursing infants have unknown potential for adverse events secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with SL-401 and azacitidine.
  • Infection is a common feature of AML. Patients with active infection are permitted to enroll provided that the infection is controlled. Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control

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): NCT03113643

Contact: Andrew Lane, MD, PhD 617-632-4589

United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Anthony Stein, MD    626-359-8111   
Principal Investigator: Anthony Stein, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Andrew Lane, MD, PhD    617-632-4589   
Principal Investigator: Andrew Lane, MD, PhD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Naveen Pemmaraju, MD    713-792-4956   
Principal Investigator: Naveen Pemmaraju, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Stemline Therapeutics, Inc.
Principal Investigator: Andrew Lane, MD, PhD Dana-Farber Cancer Institute

Responsible Party: Andrew Lane, Andrew Lane, MD, PhD, Dana-Farber Cancer Institute Identifier: NCT03113643     History of Changes
Other Study ID Numbers: 17-056
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andrew Lane, Dana-Farber Cancer Institute:
Acute Myeloid Leukemia
Myelodysplastic Syndrome

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors