NCT04044209

A Study of the IDH1 Inhibitor AG-120 in Combination With the Checkpoint Blockade Inhibitor, Nivolumab, for Patients With IDH1 Mutated Relapsed/Refractory AML and High Risk MDS

A Phase II of the IDH1 Inhibitor AG-120 in Combination With the Checkpoint Blockade Inhibitor, Nivolumab, for Patients With IDH1 Mutated Relapsed/Refractory AML and High Risk MDS

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

In this trial the investigators aim to evaluate safety and efficacy of combination Ivosidenib (AG-120) and nivolumab in the context of adult patients with Isocitrate dehydrogenase-1 (IDH1) mutated acute myeloid leukemias (AML) or Myelodysplastic syndromes (MDS).

Detailed description

Primary objectives: 1. To determine the overall response rate of (CR/CRi) of combination ivosidenib (AG-120) and nivolumab in patients with high risk MDS and relapsed/ refractory AML 2. To determine the duration of response of combination ivosidenib (AG-120) and nivolumab in patients with high risk MDS and relapsed/ refractory AML 2.2 Secondary Objectives 1\) To determine the progression free survival of patients treated with combination ivosidenib (AG- 120) and nivolumab. 2) To determine the overall survival of patients treated with combination ivosidenib (AG-120) and nivolumab. 3) To determine hematological response rate of patients treated with combination ivosidenib (AG- 120) and nivolumab. 4) To establish the duration of response to treatment of patients treated with combination ivosidenib (AG-120) and nivolumab. 5) To evaluate the safety and tolerability of combination ivosidenib (AG-120) and nivolumab. Exploratory objectives: 1. To assess the relationship between treatment response and correlative studies such as plasma and bone marrow 2-HG levels, and IDH variant allele frequency. 2. Genomic characterization by assaying specimens obtained from patients using an MDS/AML specific panel through the duration of therapy to longitudinally assess mutational burden before and during therapy, and correlating this mutational data with patient outcomes 3. Correlate exploratory biomarkers including PD-L1 expression, circulating myeloid-derived suppressor cells and interferon gamma signatures to response

Conditions

• Myelodysplastic Syndromes
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	AG-120	The IDH1 inhibitor ivosidenib (AG-120) that will be administered orally on a continuous basis at the dose of 500 mg/day starting at day 1 of each cycle. A cycle will be defined as a 28-day period.
DRUG	Nivolumab	On Cycle 2 day 1 the patient will receive nivolumab 480mg once. This will be repeated on Day 1 of every subsequent cycle.

Timeline

• Start date: 2020-02-12
• Primary completion: 2021-09-01
• Completion: 2023-09-01
• First posted: 2019-08-05
• Last updated: 2022-01-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study