Clinical Trials /

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

NCT03113643

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 17-056
  • NCT ID: NCT03113643

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
AzacitidineVidazaSL-401+ Azacitidine
SL-401SL-401+ Azacitidine

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
SL-401+ AzacitidineExperimentalSL-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
  • Azacitidine
  • SL-401

Eligibility Criteria

        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)

        OR

        --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)

        OR

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Complete Response Rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to response and duration of response
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome

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