Clinical Trials /

SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax 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 - Venetoclax

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 or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)
  • Official Title: Phase 1 Study of SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia (AML) or in Treatment-Naive Subjects With AML Not Eligible for Standard Induction 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
VenetoclaxVenclyxto, VenclextaSL-401+ Azacitidine + Venetoclax

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 - Venetoclax

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 and venetoclax as a
      treatment option for AML. This regimen has not been approved for MDS. SL-401 has not been FDA
      approved for your specific disease, but it has been approved for other uses.

      In this research study, the study drug SL-401 will be combined with the standard dose of
      azacitidine (for MDS patients) or azacitidine/venetoclax (for AML patients). The goal of this
      research study is to try and determine the safest, highest dose of study drug, SL-401, in
      combination with azacitidine or azacitidine/venetoclax 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 your 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 or azacitidine/venetoclax, affects certain proteins in your
      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
SL-401+ Azacitidine + VenetoclaxExperimentalSL-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; Venetoclax will be administered for 21 days on a 28 day cycle; Venetoclax will be taken orally
  • Azacitidine
  • SL-401
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of acute myeloid leukemia (AML) [Cohort B] or
             myelodysplastic syndrome (MDS) [Cohort A] 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) [Cohort B] OR Age >= 18 years with treatment-naïve AML who decline
             intensive induction chemotherapy or who are unfit due to co-morbidity or other factors
             (see APPENDIX A for unfitness definitions) (hydroxyurea is not considered a prior
             treatment regimen) [Cohort B] OR Age >= 18 years with MDS and >= 10% myeloblasts in
             the bone marrow [Cohort A]

          -  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 < 1.5x ULN (if thought to be > 1.5x 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

          -  [Cohort B] WBC < 10,000 / uL on day of first therapy, cytoreduction may be achieved
             using hydroxyurea

          -  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 protocol
             treatment. 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
             protocol treatment.

        Exclusion Criteria:

          -  Prior treatment with SL-401 [Cohort A or B] or venetoclax [Cohort B]

          -  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

          -  [Cohort B] Patients with gastrointestinal (GI) tract disease causing the inability to
             take oral medication, malabsorption syndrome, a requirement for intravenous (IV)
             alimentation, prior surgical procedures affecting absorption, uncontrolled
             inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)

          -  [Cohort B] Patients on strong CYP3A inducers within 7 days of first dose of study
             treatment.
      
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:To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax in this patient population and evaluate the safety of this regimen

Secondary Outcome Measures

Measure:Complete Response Rate
Time Frame:2 years
Safety Issue:
Description:To estimate the complete remission (CR) / CR with incomplete count recovery (CRi) rate within 6 cycles of combination therapy consisting of SL-401 administered with azacitidine or in combination with azacitidine and venetoclax in subjects with AML and high-risk MDS
Measure:Time to response
Time Frame:2 years
Safety Issue:
Description:To estimate the time to response with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Measure:Duration of remission
Time Frame:2 years
Safety Issue:
Description:To estimate the duration of remission with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Measure:Progression Free Survival
Time Frame:1 and 2 years
Safety Issue:
Description:To estimate the 1 and 2-year progression free survival (PFS) with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:To estimate the overall survival (OS) with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax

Details

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

Trial Keywords

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome

Last Updated

April 6, 2020