SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Related Clinical Trial
SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Graft Versus Host Disease-Reduction Strategies for Donor Blood Stem Cell Transplant Patients With Acute Leukemia Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies PH 1 Study to Evaluate Safety and Tolerability of XmAb14045 in Patients With CD123-expressing Hematologic Malignancies Trial to Evaluate the Safety and Efficacy of MB-102 in Patients With BPDCN, AML, and hrMDS. Descriptive Study of the Efficacy of Treatments for Blastic Dendritic Cell Neoplasm (BPDCN) Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm Study of IMGN632 in Patients With Relapse/Refractory AML, BPDCN, ALL, Other CD123+ Hem Malignancies Study of Venetoclax, a BCL2 Antagonist, for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Blastic Plasmacytoid Dendritic Cell Neoplasm in Korean Population. Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN SL-401 in Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm or Acute Myeloid Leukemia

Brief Title

SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Official Title

Phase 1 Study of SL-401 in Combination With Azacitidine and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia (AML) and in Treatment-Naive Subjects With AML Not Eligible for Standard Induction and in Subjects With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) or SL-401 in Combination With Azacitidine in Subjects With High-Risk Myelodysplastic Syndrome (MDS)

Brief Summary

      This research study is studying a drug as a possible treatment for diagnosis of AML, BPDCN
      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. However, the combination of these two drugs with SL-401 has not
      been FDA approved.

      The combination of SL-401, azacitidine and venetoclax has not been FDA approved for BPDCN.
      However, SL-401 has been FDA approved for BPDCN.

      The combination of SL-401 and azacitidine has not been FDA approved for BPDCN.

      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 and BPDCN 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, BPDCN 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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Maximum Tolerated Dose

Secondary Outcome

 Complete Response Rate

Condition

Acute Myeloid Leukemia

Intervention

Azacitidine

Study Arms / Comparison Groups

 SL-401+ Azacitidine
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

72

Start Date

June 26, 2017

Completion Date

May 31, 2024

Primary Completion Date

May 31, 2022

Eligibility Criteria

        Inclusion Criteria:

        Histologically confirmed diagnosis of acute myeloid leukemia (AML) [Cohort B] or
        myelodysplastic syndrome (MDS) [Cohort A] or BPDCN [Cohort C] per 2016 WHO criteria

        CD123 / IL3RA expression on the subject's AML or MDS blasts or BPDCN cells 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]

        OR

        Age >= 18 years with relapsed or refractory BPDCN (hydroxyurea is not considered a prior
        treatment regimen) [Cohort C]

        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

        [Cohorts B and C] WBC < 20,000 / 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 venetoclax [Cohorts B or C], unless it was last taken >2 months before
        protocol therapy

        Diagnosis of acute promyelocytic leukemia

        Received treatment with chemotherapy, radiation, or biologic cancer therapy within 14 days
        of first protocol treatment, except for intrathecal chemotherapy. Prior and concurrent
        hydroxyurea is permitted.

        Hematopoietic stem cell transplantation (HSCT) within 60 days of screening or active graft
        versus-host-disease

        Active CNS involvement by AML or BPDCN. Screening lumbar puncture (LP) required for
        patients with BPDCN. If history of treated CNS involvement, must have had two consecutive
        negative LPs since last CNS involvement, which may include the screening LP

        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, azacitidine, and venetoclax
        (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,
        azacitidine, and venetoclax.

        Patients with uncontrolled infection shall not be enrolled until infection is treated and
        brought under control. Patients with active infection are permitted to enroll provided that
        the infection is controlled

        [Cohorts B and C] 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)

        [Cohorts B and C] Patients on strong CYP3A inducers within 7 days of first dose of study
        treatment.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Andrew Lane, MD, PhD, 617-632-4589, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03113643

Organization ID

17-056


Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute

Collaborators

 Stemline Therapeutics, Inc.

Study Sponsor

Andrew Lane, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute


Verification Date

January 2021