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)

NCT03113643 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17-056
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 3

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

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Blastic Plasmacytoid Dendritic Cell Neoplasm

Keywords

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Blastic Plasmacytoid Dendritic Cell Neoplasm; BPDCN

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  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

  2 years

Secondary Outcomes (5)

• Complete Response Rate

  2 years

• Time to response

  2 years

• Duration of remission

  2 years

• Progression Free Survival

  1 and 2 years

• Overall Survival

  2 years

Study Arms (2)

SL-401+ Azacitidine

EXPERIMENTAL

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; Drug: SL-401

SL-401+ Azacitidine + Venetoclax

EXPERIMENTAL

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; Venetoclax will be administered for 21 days on a 28 day cycle; Venetoclax will be taken orally

Drug: Azacitidine; Drug: SL-401; Drug: Venetoclax

Interventions

Azacitidine DRUG

Chemotherapy

Also known as: Vidaza

SL-401+ Azacitidine; SL-401+ Azacitidine + Venetoclax

SL-401 DRUG

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.

SL-401+ Azacitidine; SL-401+ Azacitidine + Venetoclax

Venetoclax DRUG

Venetoclax is a BH3-mimetic. Venetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. Overexpression of Bcl-2 in some lymphoid malignancies has sometimes shown to be linked with increased resistance to chemotherapy.

Also known as: Venclyxto, Venclexta

SL-401+ Azacitidine + Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \[Cohort B\]
• 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) \[Cohort B\]
• Age \>= 18 years with MDS and \> 10% myeloblasts in the bone marrow \[Cohort A\]
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Stemline Therapeutics, Inc.: collaborator

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (2)

• Lane AA, Garcia JS, Raulston EG, Garzon JL, Galinsky I, Baxter EW, Leonard R, DeAngelo DJ, Luskin MR, Reilly CR, Stahl M, Stone RM, Vedula RS, Wadleigh MM, Winer ES, Mughal T, Brooks C, Gupta IV, Stevenson KE, Neuberg DS, Ren S, Keating J, Konopleva M, Stein A, Pemmaraju N. Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia. Blood Adv. 2024 Feb 13;8(3):591-602. doi: 10.1182/bloodadvances.2023011721.

  PMID: 38052038 DERIVED

• Wang SY, Thomassen K, Kurch L, Opitz S, Franke GN, Bach E, Platzbecker U, Kayser S. Combination of Tagraxofusp and Azacitidine Is an Effective Option for Relapsed Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem-Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Jul;21(7):e579-e582. doi: 10.1016/j.clml.2021.02.008. Epub 2021 Mar 2. No abstract available.

  PMID: 33795208 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

Azacitidine; tagraxofusp; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Andrew Lane, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Lane, MD, PhD

CONTACT

857-215-1405; andrew_lane@dfci.harvard.edu

Veronica Zehnder

CONTACT

veronica_zehnder@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Andrew Lane, MD, PhD

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 13, 2017
• Study Start: June 26, 2017
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)