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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)

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Azacitidine
SL-401
Venetoclax
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Myelodysplastic Syndrome, Blastic Plasmacytoid Dendritic Cell Neoplasm, BPDCN

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • City of HopeRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

SL-401+ Azacitidine

SL-401+ Azacitidine + Venetoclax

Arm 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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Complete Response Rate
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
Time to response
To estimate the time to response with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Duration of remission
To estimate the duration of remission with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Progression Free Survival
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
Overall Survival
To estimate the overall survival (OS) with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax

Full Information

First Posted
April 10, 2017
Last Updated
June 19, 2023
Sponsor
Dana-Farber Cancer Institute
Collaborators
Stemline Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03113643
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 26, 2017 (Actual)
Primary Completion Date
May 31, 2024 (Anticipated)
Study Completion Date
May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Stemline Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndrome, Blastic Plasmacytoid Dendritic Cell Neoplasm
Keywords
Acute Myeloid Leukemia, Myelodysplastic Syndrome, Blastic Plasmacytoid Dendritic Cell Neoplasm, BPDCN

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SL-401+ Azacitidine
Arm Type
Experimental
Arm 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
Arm Title
SL-401+ Azacitidine + Venetoclax
Arm Type
Experimental
Arm 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; Venetoclax will be administered for 21 days on a 28 day cycle; Venetoclax will be taken orally
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
Chemotherapy
Intervention Type
Drug
Intervention Name(s)
SL-401
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclyxto, Venclexta
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Complete Response Rate
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
Time Frame
2 years
Title
Time to response
Description
To estimate the time to response with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Time Frame
2 years
Title
Duration of remission
Description
To estimate the duration of remission with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Time Frame
2 years
Title
Progression Free Survival
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
Time Frame
1 and 2 years
Title
Overall Survival
Description
To estimate the overall survival (OS) with SL-401 in combination with azacitidine or in combination with azacitidine and venetoclax
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrew Lane, MD, PhD
Phone
617-632-4589
Email
andrew_lane@dfci.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Lane, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anthony Stein, MD
Phone
626-359-8111
Email
AStein@coh.org
First Name & Middle Initial & Last Name & Degree
Anthony Stein, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Lane, MD, PhD
Phone
617-582-7386
Email
andrew_lane@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Andrew Lane, MD, PhD
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naveen Pemmaraju, MD
Phone
713-792-4956
Email
npemmaraju@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Naveen Pemmaraju, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33795208
Citation
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.
Results Reference
derived

Learn more about this 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)

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