A Study of an IDH1m Inhibitor in Participants With IDH1-Mutated Malignancies and Hepatic or Renal Impairment
18 Years and older, Male and Female
S095031-218 (primary)
NCI-2025-07166
2024-517923-38-00
Summary
The objective of this study is to investigate the PK, PD, safety, and tolerability of
ivosidenib in adult participants with IDH1-mutated malignancies and hepatic impairment
(HI)/ renal impairment (RI). Participants will be enrolled into one of 5 groups based on
their hepatic or renal function. During the treatment period participants will have study
visits on days 1, 4, 8, 15, 22, and 28 of Cycle 1, on days 1 and 15 of Cycle 2 and 3, and
on day 1 of each additional cycle. Each cycle is 28 consecutive days of treatment and
cycles will be continuous until the end of the study. Approximately 30 days after
treatment has ended, a safety follow-up visit will occur. Study visits may include blood
tests, ECG, vital signs, and a physical examination.
Eligibility
- Participants with hematologic malignancies (including but not limited to acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms, clonal cytopenia of unknown significance with a high-risk score [CHRS =12.5], chronic myelomonocytic leukemia, multiple myeloma, and non-Hodgkin's lymphoma) or solid tumors excluding glioma, with a locally confirmed IDH1 R132 mutation before Cycle 1 Day 1.
- Based on renal and hepatic function, participants within the: a. Moderate HI group, must have: i. Total bilirubin >1.5 to 3 × upper limit of normal (ULN), not linked to Gilbert's disease, and any aspartate aminotransferase (AST) value, ii. Adequate renal function as evidenced by creatinine clearance (CrCl) =60 mL/min estimated according to the Cockcroft-Gault formula. b. Severe HI group, must have: i. Total bilirubin >3 × ULN and any AST value, ii. Adequate renal function as evidenced by CrCl =60 mL/min estimated according to the Cockcroft-Gault formula. c. Severe RI group, must have: i. CrCl =15 to 29 mL/min estimated according to the Cockcroft-Gault formula, ii. Adequate hepatic function as evidenced by:
- Blood total bilirubin =1.5 × ULN, unless due to Gilbert's disease, where participants should have blood total bilirubin =3 × ULN;
- AST, alanine aminotransferase, and alkaline phosphatase =3.0 × ULN
- Participants of the control groups with adequate hepatic or renal function characterized as:
- Hepatic control group: Adequate hepatic function as evidenced by total bilirubin and AST =ULN, and normal to mild RI (CrCl =60 mL/min estimated according to the Cockcroft-Gault formula).
- Renal control group: Adequate renal function as evidenced by CrCl =90 mL/min (estimated according to the Cockcroft-Gault formula) and normal to mild HI (total bilirubin =1.5 × ULN, participants with Gilbert's disease should have blood total bilirubin =3 × ULN).
- Participants previously or currently treated with ivosidenib are eligible if treated at the 500 mg QD dose or if treated at the 250 mg QD dose due to strong cytochrome P450 (CYP)3A4 inhibitor intake. Participants with a hematologic malignancy on co-treatment with azacitidine are also eligible.
- WOCBP must agree to abstain from sexual intercourse or use 2 effective methods of birth control (a highly effective method and a barrier method) from the time of giving informed consent throughout the study and for 90 days after the last dose of ivosidenib. Hormonal contraception alone is not considered an acceptable method of contraception and should be combined with a barrier method.
Treatment Sites in Georgia
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