WithdrawnPhase 1/2

ASTX727 and FT-2102 in Treating IDH1-Mutated Recurrent/Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

Stopped: Loss of funding

0Started 2019-08-27

Plain-language summary

This phase Ib/II trial studies the side effects and best dose of FT-2102 when given together with ASTX727 in treating patients with IDH1-mutated myelodysplastic syndrome or acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). ASTX727 is an oral deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor. DNA methylation is necessary for cell differentiation and development. Changes to the methylation profile can lead to DNA instability which can cause diseases like cancer. DNMT inhibitors target and inhibit these changes. FT-2102 is an isocitrate dehydrogenase 1 (IDH1) inhibitor. IDH1 is a type of protein involved in metabolism, or the process of providing the body's cells with energy. FT-2102 may stop the abnormal IDH1 protein and may reduce 2-HG levels in diseased cells to levels found in normal cells. Giving ASTX727 and FT-2102 may work better in treating patients with myelodysplastic syndrome or acute myeloid leukemia compared to ASTX727 and FT-2102 alone.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Must voluntarily sign an informed consent document (ICF) * Morphologically confirmed diagnosis of MDS (inclusive of MDS/MPN) or AML in accordance with World Health Organization (WHO) diagnostic criteria * Phase Ib: Subjects may have * Relapsed/refractory AML or MDS or * Treatment naive AML * Phase II Expansion: Subjects may have * Relapsed/refractory AML or MDS or * Treatment naive AML or * Treatment naive MDS * For patients with MDS, must have a Revised International Prognostics Scoring System (IPSS-R) risk category of intermediate, high, or very high * Confirmed IDH1 R132 mutation * A bone marrow biopsy must be performed and tissue collected for entrance to the trial * Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Life expectancy of at least 3 months in the assessment of the investigator * Recovery from the non-hematologic toxic effects of prior treatment to grade =\< 1, or baseline value according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 classification (excluding infertility, alopecia, or grade 1 neuropathy) * Must have adequate hepatic and renal function as demonstrated by the following: ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN); Direct bilirubin ≤ 1.5 x ULN(or ≤ 2x ULN if due to Gilbert's disease); Serum creatinine of 1.5 x ULN or creatinine clearance of \> 50 mL/min (whichever is lower) * Baseline Frideri…

What they're measuring

Incidence of adverse events (Phase Ib)

Timeframe: Up to 30 days

Response rate (Phase II)

Timeframe: Approximately 12 months

Trial details

NCT IDNCT04013880

SponsorVanderbilt-Ingram Cancer Center

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2021-03-31