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A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation (AUGMENT-101)

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Mixed Lineage Acute Leukemia

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SNDX-5613
cobicistat
Sponsored by
Syndax Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, ALL, MPAL, MLAL, ALAL, relapsed leukemia, refractory leukemia, acute leukemia, MLLr, KMT2A, NPM1

Eligibility Criteria

30 Days - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have active acute leukemia (bone marrow blasts ≥ 5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020), or acute leukemia harboring an MLL rearrangement, NUP98 rearrangement, or NPM1 mutation that have detectable disease in the bone marrow.

  1. Phase 1:

    • Arm A: Patients not receiving any strong CYP3A4 inhibitor/inducers or fluconazole.
    • Arm B: Patients receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.
    • Arm C: Patients receiving SNDX-5613 in combination with cobicistat.
    • Arm D: Patients receiving fluconazole (moderate CYP3A4 inhibitor).
    • Arm E: Patients not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.
    • Arm F: Patients receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.
  2. Phase 2:

    • Cohort 2A: Documented R/R ALL/MPAL with an MLLr translocation.
    • Cohort 2B: Documented R/R AML with an MLLr translocation.
    • Cohort 2C: Documented R/R AML with NPM1c.
  3. White blood cell count below 25,000/ microliter at time of enrollment. Patients may receive cytoreduction prior to enrollment per protocol-specified criteria.
  4. Male or female patient aged ≥30 days old.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥40.
  6. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 neuropathy or alopecia.
  7. Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
  8. Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion.
  9. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy.
  10. Myelosuppressive Chemotherapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of cytotoxic/myelosuppressive therapy.
  11. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
  12. Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent.
  13. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy.
  14. Adequate organ function.
  15. If of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.

Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for study participation:

  1. Active diagnosis of acute promyelocytic leukemia.
  2. Isolated extramedullary relapse.
  3. Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic).
  4. Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Patients with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment.
  5. Hepatitis B or C.
  6. Pregnant or nursing women.
  7. Cardiac Disease:

    Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.

    - Corrected QT interval (QTc) >450 milliseconds.

  8. Gastrointestinal Disease:

    • Chronic diarrhea or other gastrointestinal issue that might affect oral drug absorption or ingestion (ie, short-gut syndrome, gastroparesis, etc).
    • Cirrhosis with a Child-Pugh score of B or C.
  9. Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant patients must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Patients may be on physiological doses of steroids.
  10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy, or concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the patient is not receiving any systemic therapy or radiation.
  11. In Phase 1 and Phase 2: Patients requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (eg, diphenhydramine, famotidine, ondansetron, Bactrim) and the azoles permitted in the relevant arms of Phase 1.

Sites / Locations

  • City of Hope Comprehensive Cancer CenterRecruiting
  • Stanford Cancer InstituteRecruiting
  • University of ColoradoRecruiting
  • Florida Cancer Specialists and Research InstituteRecruiting
  • Moffitt Cancer Center
  • Emory Winship Cancer InstituteRecruiting
  • Children's Healthcare of AtlantaRecruiting
  • The University of Chicago Medical CenterRecruiting
  • University of Iowa hospitalRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • Washington University in St. Louis School of MedicineRecruiting
  • Hackensack University Medical CenterRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Montefiore Medical CenterRecruiting
  • University of CincinnatiRecruiting
  • Ohio State UniversityRecruiting
  • Oregon Health & Science UniversityRecruiting
  • University of PennsylvaniaRecruiting
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • Huntsman Cancer Institute at the University of UtahRecruiting
  • Peter MacCallum Cancer Centre (PMCC)Recruiting
  • Alfred HospitalRecruiting
  • Sir Charles Gairdner HospitalRecruiting
  • Royal North Shore HospitalRecruiting
  • Princess Margaret Cancer CentreRecruiting
  • University Health NetworkRecruiting
  • The Hospital for Sick ChildrenRecruiting
  • Centre Hospitalier Lyon SudRecruiting
  • Hadassah Medical Center- Ein KeremRecruiting
  • Princess Maxima Center for Pediatric OncologyRecruiting
  • Hospital Universitari I Politècnic La Fe Avinguda Fernando Abril MartorellRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental: SNDX-5613

Arm Description

Phase 1: Oral SNDX-5613; sequential cohorts of escalating dose levels of SNDX-5613 to identify the MTD and RP2D. Participants will be enrolled in 1 of 6 dose-escalation arms: Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis Arm C: Participants receiving SNDX-5613 and cobicistat Arm D: Participants receiving fluconazole for antifungal prophylaxis Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers Arm F: Participants receiving isavuconazole for antifungal prophylaxis Phase 2: Oral SNDX-5613; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows: Cohort 2A: Participants with MLLr ALL/MPAL Cohort 2B: Participants with MLLr AML Cohort 2C: Participants with NPM1c AML

Outcomes

Primary Outcome Measures

Occurrence of dose-limiting toxicities (DLTs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Frequency, duration, and severity of treatment-related TEAEs (TRAEs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Frequency, duration, and severity of serious adverse events (SAEs) (Phase 1)
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Cmax (Phase 1)
Maximum plasma concentration (CMAX) of SNDX-5613 (Phase 1)
Tmax (Phase 1)
Time to observed maximum plasma concentration of SNDX-5613 (Phase 1)
AUC0-t (Phase 1)
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of SNDX-5613 (Phase 1)
AUC0-24 (Phase 1)
Area under the plasma concentration-time curve from time 0 to 24 hours (Phase 1)
CL/F (Phase 1)
Apparent oral clearance of SNDX-5613 (Phase 1)
Vz/F (Phase 1)
Apparent volume of distribution of SNDX-5613 (Phase 1)
t1/2 (Phase 1)
Terminal phase half-life of SNDX-5613 (Phase 1)
Complete remission (CR) rate (Phase 2)
To assess the CR rate (CR+CRh). (Phase 2)
Frequency and severity of adverse events (AEs) (Phase 2)
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Frequency and severity of serious adverse events (SAEs) (Phase 2)
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs) (Phase 2)
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Frequency, duration, and severity of treatment-related TEAEs (TRAEs) (Phase 2)
Assessed by the NCI CTCAE version 5.0 (Phase 2)

Secondary Outcome Measures

Composite definition of complete remission (CRc) Rate (Phase 2)
To assess the CRc rate. (Phase 2)
Complete remission with partial hematologic recovery (CR+CRh) rate after 4 weeks of therapy (Phase 2)
To assess the CR (CR+CRh) rate after 4 weeks of therapy. (Phase 2)
BORR (CRc+ partial remission [PR]). (Phase 2)
To assess the best overall remission rate (BORR) of SNDX-5613 (Phase 2)
Median RFS (Phase 2)
To assess relapse-free survival of SNDX-5613 (Phase 2)
TTR (Phase 2)
To assess the time to response (TTR) of SNDX-5613 (Phase 2)
DOR (Phase 2)
To assess the duration of response (DOR) of SNDX-5613 (Phase 2)
OS (Phase 2)
To assess overall survival of SNDX-5613 (Phase 2)
Cmax (Phase 2)
Maximum plasma concentration (CMAX) of SNDX-5613 (Phase 2)
Tmax (Phase 2)
Time to observed maximum plasma concentration of SNDX-5613 (Phase 2)
AUC0-t (Phase 2)
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of SNDX-5613 (Phase 2)
AUC0-24 (Phase 2)
Area under the plasma concentration-time curve from time 0 to 24 hours (Phase 2)
CL/F (Phase 2)
Apparent oral clearance of SNDX-5613 (Phase 2)
Vz/F (Phase 2)
Apparent volume of distribution of SNDX-5613 (Phase 2)
t1/2 (Phase 2)
Terminal phase half-life of SNDX-5613 (Phase 2)

Full Information

First Posted
August 16, 2019
Last Updated
August 17, 2023
Sponsor
Syndax Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04065399
Brief Title
A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation
Acronym
AUGMENT-101
Official Title
A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 5, 2019 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Syndax Pharmaceuticals

4. Oversight

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

5. Study Description

Brief Summary
Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of SNDX-5613 in participants with acute leukemia. In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613.
Detailed Description
Phase 1: Oral SNDX-5613; sequential cohorts of escalating dose levels of SNDX-5613 to identify the MTD and RP2D. Participants will be enrolled in one of six dose-escalation arms: Arm A: Participants not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers or fluconazole. Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis. Arm C: Participants receiving SNDX-5613 and cobicistat. Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis. Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers. Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis. In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613: Cohort 2A: Participants with MLLr acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL) Cohort 2B: Participants with MLLr AML Cohort 2C: Participants with NPM1c AML

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Mixed Lineage Acute Leukemia, Mixed Phenotype Acute Leukemia, Acute Leukemia of Ambiguous Lineage
Keywords
AML, ALL, MPAL, MLAL, ALAL, relapsed leukemia, refractory leukemia, acute leukemia, MLLr, KMT2A, NPM1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase 1 will employ an accelerated titration design. The dose escalation will follow a modified Fibonacci sequence.
Masking
None (Open Label)
Allocation
N/A
Enrollment
440 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: SNDX-5613
Arm Type
Experimental
Arm Description
Phase 1: Oral SNDX-5613; sequential cohorts of escalating dose levels of SNDX-5613 to identify the MTD and RP2D. Participants will be enrolled in 1 of 6 dose-escalation arms: Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis Arm C: Participants receiving SNDX-5613 and cobicistat Arm D: Participants receiving fluconazole for antifungal prophylaxis Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers Arm F: Participants receiving isavuconazole for antifungal prophylaxis Phase 2: Oral SNDX-5613; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows: Cohort 2A: Participants with MLLr ALL/MPAL Cohort 2B: Participants with MLLr AML Cohort 2C: Participants with NPM1c AML
Intervention Type
Drug
Intervention Name(s)
SNDX-5613
Intervention Description
SNDX-5613 orally
Intervention Type
Drug
Intervention Name(s)
cobicistat
Intervention Description
Phase 1 Arm C participants will receive 150 mg cobicistat daily.
Primary Outcome Measure Information:
Title
Occurrence of dose-limiting toxicities (DLTs) (Phase 1)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Time Frame
Approximately 1 year
Title
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs) (Phase 1)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Time Frame
Approximately 1 year
Title
Frequency, duration, and severity of treatment-related TEAEs (TRAEs) (Phase 1)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Time Frame
Approximately 1 year
Title
Frequency, duration, and severity of serious adverse events (SAEs) (Phase 1)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 1)
Time Frame
Approximately 1 year
Title
Cmax (Phase 1)
Description
Maximum plasma concentration (CMAX) of SNDX-5613 (Phase 1)
Time Frame
Approximately 1 year
Title
Tmax (Phase 1)
Description
Time to observed maximum plasma concentration of SNDX-5613 (Phase 1)
Time Frame
Approximately 1 year
Title
AUC0-t (Phase 1)
Description
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of SNDX-5613 (Phase 1)
Time Frame
Approximately 1 year
Title
AUC0-24 (Phase 1)
Description
Area under the plasma concentration-time curve from time 0 to 24 hours (Phase 1)
Time Frame
Approximately 1 year
Title
CL/F (Phase 1)
Description
Apparent oral clearance of SNDX-5613 (Phase 1)
Time Frame
Approximately 1 year
Title
Vz/F (Phase 1)
Description
Apparent volume of distribution of SNDX-5613 (Phase 1)
Time Frame
Approximately 1 year
Title
t1/2 (Phase 1)
Description
Terminal phase half-life of SNDX-5613 (Phase 1)
Time Frame
Approximately 1 year
Title
Complete remission (CR) rate (Phase 2)
Description
To assess the CR rate (CR+CRh). (Phase 2)
Time Frame
Approximately 3 years
Title
Frequency and severity of adverse events (AEs) (Phase 2)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Time Frame
Approximately 3 years
Title
Frequency and severity of serious adverse events (SAEs) (Phase 2)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Time Frame
Approximately 3 years
Title
Frequency, duration, and severity of treatment-emergent adverse events (TEAEs) (Phase 2)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Time Frame
Approximately 3 years
Title
Frequency, duration, and severity of treatment-related TEAEs (TRAEs) (Phase 2)
Description
Assessed by the NCI CTCAE version 5.0 (Phase 2)
Time Frame
Approximately 3 years
Secondary Outcome Measure Information:
Title
Composite definition of complete remission (CRc) Rate (Phase 2)
Description
To assess the CRc rate. (Phase 2)
Time Frame
Approximately 3 years
Title
Complete remission with partial hematologic recovery (CR+CRh) rate after 4 weeks of therapy (Phase 2)
Description
To assess the CR (CR+CRh) rate after 4 weeks of therapy. (Phase 2)
Time Frame
Approximately 19 months
Title
BORR (CRc+ partial remission [PR]). (Phase 2)
Description
To assess the best overall remission rate (BORR) of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
Median RFS (Phase 2)
Description
To assess relapse-free survival of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
TTR (Phase 2)
Description
To assess the time to response (TTR) of SNDX-5613 (Phase 2)
Time Frame
Approximately 34 months
Title
DOR (Phase 2)
Description
To assess the duration of response (DOR) of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
OS (Phase 2)
Description
To assess overall survival of SNDX-5613 (Phase 2)
Time Frame
Approximately 5 years
Title
Cmax (Phase 2)
Description
Maximum plasma concentration (CMAX) of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
Tmax (Phase 2)
Description
Time to observed maximum plasma concentration of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
AUC0-t (Phase 2)
Description
Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
AUC0-24 (Phase 2)
Description
Area under the plasma concentration-time curve from time 0 to 24 hours (Phase 2)
Time Frame
Approximately 3 years
Title
CL/F (Phase 2)
Description
Apparent oral clearance of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
Vz/F (Phase 2)
Description
Apparent volume of distribution of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years
Title
t1/2 (Phase 2)
Description
Terminal phase half-life of SNDX-5613 (Phase 2)
Time Frame
Approximately 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants must have active acute leukemia (bone marrow blasts ≥5% or reappearance of blasts in peripheral blood) as defined by the National Comprehensive Cancer Network (NCCN) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (Version 1.2020) and Acute Myeloid Leukemia (Version 3.2020), or acute leukemia harboring an MLL rearrangement, NUP98 rearrangement, or NPM1c mutation that have detectable disease in the bone marrow. Phase 1: Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole. Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis. Arm C: Participants receiving SNDX-5613 in combination with cobicistat. Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor). Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers. Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis. Phase 2: Cohort 2A: Documented R/R ALL/MPAL with an MLLr translocation. Cohort 2B: Documented R/R AML with an MLLr translocation. Cohort 2C: Documented R/R AML with NPM1c. White blood cell count below 25,000/ microliter at time of enrollment. Participants may receive cytoreduction prior to enrollment per protocol-specified criteria. Male or female participants aged ≥30 days old. Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or Karnofsky/Lansky score ≥50. Any prior treatment-related toxicities resolved to ≤Grade 1 prior to enrollment, with the exception of ≤Grade 2 neuropathy or alopecia. Radiation Therapy: At least 60 days from prior total body irradiation (TBI), craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port). Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy. Antileukemia Therapy: At least 14 days, or 5 half-lives, whichever is shorter, since the completion of antileukemic therapy. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors. Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the completion of therapy with an antineoplastic biologic agent. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy. Adequate organ function. If of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose. Exclusion Criteria: Participants meeting any of the following criteria are not eligible for study participation: Active diagnosis of acute promyelocytic leukemia. Isolated extramedullary relapse. Active central nervous system disease (cytologic, such as any blasts on cytospin, or radiographic). Detectable human immunodeficiency virus (HIV) viral load within the previous 6 months. Participants with a known history of HIV 1/2 antibodies must have viral load testing prior to study enrollment. Hepatitis B or C. Pregnant or nursing women. Cardiac Disease: Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. - Corrected QT interval (QTc) >450 milliseconds. Gastrointestinal Disease: any gastrointestinal issue of the upper GI tract that might affect oral drug absorption or ingestion (that is, gastric bypass, gastroparesis, etc). Cirrhosis with a Child-Pugh score of B or C. Graft-Versus-Host Disease (GVHD): Signs or symptoms of acute or chronic GVHD >Grade 0 within 4 weeks of enrollment. All transplant participants must have been off all systemic immunosuppressive therapy and calcineurin inhibitors for at least 4 weeks prior to enrollment. Participants may be on physiological doses of steroids. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (for example, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy, or concurrent low-grade lymphoma, that is asymptomatic and lacks bulky disease and shows no evidence of progression, and for which the participant is not receiving any systemic therapy or radiation. In Phase 1 and Phase 2: Participants requiring the concurrent use of medications known or suspected to prolong the QT/QTc interval, with the exception of drugs with low risk of QT/QTc prolongation that are used as standard supportive therapies (for example, diphenhydramine, famotidine, ondansetron, Bactrim) and the azoles permitted in the relevant arms of Phase 1.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Syndax Pharmaceuticals
Phone
781-419-1400
Email
clinicaltrials@syndax.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicole McNeer, M.D.
Organizational Affiliation
Syndax Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
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
Manjyot Nanhwan
Email
mnanhwan@coh.org
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyle Denzel Cobarrubias
Email
kcobarru@stanford.edu
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katelyn Anttila
Email
Katelyn.Anttila@ucdenver.edu
Facility Name
Florida Cancer Specialists and Research Institute
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Terri Peterson, RN
Email
tpeterson@flcancer.com
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33162
Country
United States
Individual Site Status
Completed
Facility Name
Emory Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shannon Gleason, MLS, CCRC
Phone
404-778-4334
Ext
10808
Email
shannon.gleason@emory.edu
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aflac Cancer & Blood Disorders Center Referral
Email
aflacdevtreferral@choa.org
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Howie Weiner, CCRP
Phone
773-702-2084
Facility Name
University of Iowa hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52246
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Dickens, 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
Morgan Johnson
Phone
857-215-0238
Email
Morgan_Johnson@DFCI.HARVARD.EDU
First Name & Middle Initial & Last Name & Degree
Lindsay Rae
Phone
617-582-9169
Email
Lindsey_Rae@DFCI.HARVARD.EDU
Facility Name
Washington University in St. Louis School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hannah Hartman
Phone
314-273-8628
Email
hannahlhartman@wustl.edu
First Name & Middle Initial & Last Name & Degree
Madeline Stowe
Email
mstowe@wustl.edu
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Chen, MD
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kait Tkachuk
Phone
646-608-2783
Email
tkachukk@mskcc.org
Facility Name
Montefiore Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Fehn
Email
KFEHN@montefiore.org
First Name & Middle Initial & Last Name & Degree
Joel Victor
Email
jovictor@montefiore.org
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadia Osman
Email
osmann@ucmail.uc.edu
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Molly Brandenburg
Phone
614-366-7951
Email
molly.brandenburg@osumc.edu
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
OHSU Knight Cancer Institute Clinical Trials
Email
trials@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Ronan Swords, MD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robin E Blauser, BSN RN
Phone
215-662-2870
Email
Robin.Blauser@pennmedicine.upenn.edu
Facility Name
The University of Texas 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
Ghayas Issa, MD
Email
gcissa@mdanderson.org
Facility Name
Huntsman Cancer Institute at the University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Hammond
Email
Jessica.Hammond@hci.utah.edu
First Name & Middle Initial & Last Name & Degree
Catherine Cromar
Email
Catherine.Cromar@hci.utah.edu
Facility Name
Peter MacCallum Cancer Centre (PMCC)
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Farha Inam
Email
PCCTU.HaemA@petermac.org
Facility Name
Alfred Hospital
City
Melbourne
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shaun Fleming, MD
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolyn Grove, MD
Facility Name
Royal North Shore Hospital
City
Saint Leonards
ZIP/Postal Code
2065
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Greenwood, MD
Facility Name
Princess Margaret Cancer Centre
City
Toronto
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andre Schuh
Facility Name
University Health Network
City
Toronto
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andre Schuh, MD
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aiman Siddiqi
Email
aiman.siddiqi@sickkids.ca
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Benite
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandre Deloire
Email
Alexandre.deloire@chu-lyon.fr
Facility Name
Hadassah Medical Center- Ein Kerem
City
Jerusalem
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boaz Nachmias
Facility Name
Princess Maxima Center for Pediatric Oncology
City
Utrecht
ZIP/Postal Code
3584 CS
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Secretary Trial and Data Centrum
Email
tdcsecretary@prinsesmaximacentrum.nl
Facility Name
Hospital Universitari I Politècnic La Fe Avinguda Fernando Abril Martorell
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pau Montesinos Fernandez

12. IPD Sharing Statement

Citations:
PubMed Identifier
34267079
Citation
Sasca D, Guezguez B, Kuhn MWM. Next generation epigenetic modulators to target myeloid neoplasms. Curr Opin Hematol. 2021 Sep 1;28(5):356-363. doi: 10.1097/MOH.0000000000000673.
Results Reference
derived
PubMed Identifier
33741715
Citation
Jimenez JA, Apfelbaum AA, Hawkins AG, Svoboda LK, Kumar A, Ruiz RO, Garcia AX, Haarer E, Nwosu ZC, Bradin J, Purohit T, Chen D, Cierpicki T, Grembecka J, Lyssiotis CA, Lawlor ER. EWS-FLI1 and Menin Converge to Regulate ATF4 Activity in Ewing Sarcoma. Mol Cancer Res. 2021 Jul;19(7):1182-1195. doi: 10.1158/1541-7786.MCR-20-0679. Epub 2021 Mar 19.
Results Reference
derived
Links:
URL
https://www.nature.com/articles/s41586-023-05812-3
Description
Related Info
URL
https://www.nature.com/articles/s41586-023-05755-9
Description
Related Info

Learn more about this trial

A Study of SNDX-5613 in R/R Leukemias Including Those With an MLLr/KMT2A Gene Rearrangement or NPM1 Mutation

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