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

  • STATUS
    Recruiting
  • End date
    Apr 30, 2026
  • participants needed
    440
  • sponsor
    Syndax Pharmaceuticals
Updated on 4 October 2022
cancer
myeloid leukemia
total body irradiation
acute leukemia
prednisone
blast cells
hematopoietic growth factors

Summary

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of SNDX-5613 in patients with acute leukemia.

In Phase 2, patients will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of SNDX-5613.

Description

Phase 1: Oral SNDX-5613; sequential cohorts of escalating dose levels of SNDX-5613 to identify the MTD and RP2D. Patients will be enrolled in one of six dose-escalation arms:

Arm A: Patients not receiving any strong cytochrome P450 3A4 (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 and cobicistat.

Arm D: Patients receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.

Arm E: Patients not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.

Arm F: Patients receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.

In Phase 2, patients 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: Patients with MLLr acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL).
  • Cohort 2B: Patients with MLLr AML.
  • Cohort 2C: Patients with NPM1c AML.

Details
Condition Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Mixed Lineage Acute Leukemia, Mixed Phenotype Acute Leukemia, Acute Leukemia of Ambiguous Lineage
Treatment Cobicistat, SNDX-5613
Clinical Study IdentifierNCT04065399
SponsorSyndax Pharmaceuticals
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

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
Phase 1
Arm A: Patients not receiving any strong CYP3A4 inhibitor/inducers or
Phase 2
Arm C: Patients receiving SNDX-5613 in combination with cobicistat
fluconazole
Cohort 2A: Documented R/R ALL/MPAL with an MLLr translocation
Arm B: Patients receiving itraconazole, ketoconazole, posaconazole, or
Cohort 2B: Documented R/R AML with an MLLr translocation
voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis
Cohort 2C: Documented R/R AML with NPM1c
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
Male or female patient aged ≥30 days old
antifungal prophylaxis
Eastern Cooperative Oncology Group (ECOG) performance status score 0-2 or
Karnofsky/Lansky score ≥40
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)
White blood cell count below 25,000/ microliter at time of enrollment. Patients may
craniospinal radiation and/or ≥50% radiation of the pelvis, or at least 14 days from
receive cytoreduction prior to enrollment per protocol-specified criteria
local palliative radiation therapy (small port)
Adequate organ function
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
Stem Cell Infusion: At least 60 days must have elapsed from hematopoietic stem cell
Hematopoietic Growth Factors: At least 7 days since the completion of therapy with
transplant and at least 4 weeks must have elapsed from donor lymphocyte infusion
short-acting hematopoietic growth factors and 14 days with long-acting growth factors
Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving
Myelosuppressive Chemotherapy: At least 14 days, or 5 half-lives, whichever is
physiologic dosing (equivalent to ≤10 mg prednisone daily) or cytoreductive therapy
shorter, since the completion of cytotoxic/myelosuppressive therapy
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
Biologics: At least 90 days, or 5 half-lives, whichever is shorter, since the
following the last study drug dose
completion of therapy with an antineoplastic biologic agent

Exclusion Criteria

Active diagnosis of acute promyelocytic leukemia
Isolated extramedullary relapse
Hepatitis B or C
Pregnant or nursing women
Cardiac Disease
Patients meeting any of the following criteria are not eligible for study participation
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
Active central nervous system disease (cytologic, such as any blasts on cytospin, or
Any of the following within the 6 months prior to study entry: myocardial infarction
radiographic)
uncontrolled/unstable angina, congestive heart failure (New York Heart Association
Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular
accident, or transient ischemic attack
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
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
Corrected QT interval (QTc) >450 milliseconds
enrollment. Patients 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 (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
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
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