NCT02632708

Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation

Active, enrolled Phase 1 Last updated 11 April 2025

What this trial tests

Phase 1 trial testing AG-120 in Newly Diagnosed Acute Myeloid Leukemia (AML) in 153 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

31 December 2015

Primary endpoint
13 December 2018

24 July 2026

Quick facts

Lead sponsor	Institut de Recherches Internationales Servier
Phase	Phase 1
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	153
Start date	31 December 2015
Primary completion	13 December 2018
Estimated completion	24 July 2026
Sites	17 locations across Netherlands, United States, Germany

Drugs / interventions tested

• AG-120
• AG-221 — full drug profile →
• cytarabine — full drug profile →
• daunorubicin (daunorubicin) — full drug profile →
• idarubicin (IDARUBICIN) — full drug profile →
• mitoxantrone (MITOXANTRONE) — full drug profile →
• etoposide

Conditions studied

• Newly Diagnosed Acute Myeloid Leukemia (AML) — all drugs for Newly Diagnosed Acute Myeloid Leukemia (AML) →
• Untreated AML — all drugs for Untreated AML →
• AML Arising From Myelodysplastic Syndrome (MDS) — all drugs for AML Arising From Myelodysplastic Syndrome (MDS) →
• AML Arising From Antecedent Hematologic Disorder (AHD) — all drugs for AML Arising From Antecedent Hematologic Disorder (AHD) →

Sponsor

Institut de Recherches Internationales Servier — full company profile →

Who can join

18 and older, any sex, with Newly Diagnosed Acute Myeloid Leukemia (AML) or Untreated AML. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The purpose of this Phase I, multicenter, clinical trial is to evaluate the safety of AG-120 and AG-221 when given in combination with standard AML induction and consolidation therapy. The study plans to evaluate up to 2 dose levels of AG-120 in participants with an isocitrate dehydrogenase protein 1 (IDH1) mutation and up to 2 dose levels of AG-221 in participants with an isocitrate dehydrogenase protein 2 (IDH2) mutation. AG-120 or AG-221 will be administered with 2 types of AML induction therapies (cytarabine with either daunorubicin or idarubicin) and 2 types of AML consolidation therapies (mitoxantrone with etoposide \[ME\] or cytarabine). After consolidation therapy, participants may continue on to maintenance therapy and receive daily treatment with single-agent AG-120 or AG-221 until relapse, development of an unacceptable toxicity, or hematopoietic stem cell transplant (HSCT). The study will end when all participants have discontinued study treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The emerging role and targetability of the TCA cycle in cancer metabolism.
   Anderson NM, Mucka P, Kern JG, Feng H. · · 2018 · cited 404× · PMID 28748451 · DOI 10.1007/s13238-017-0451-1
2. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia.
   Roboz GJ, DiNardo CD, Stein EM, de Botton S, et al · · 2020 · cited 284× · PMID 31841594 · DOI 10.1182/blood.2019002140
3. Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response.
   Amatangelo MD, Quek L, Shih A, Stein EM, et al · · 2017 · cited 274× · PMID 28588019 · DOI 10.1182/blood-2017-04-779447
4. Altered metabolism in cancer: insights into energy pathways and therapeutic targets.
   Tufail M, Jiang CH, Li N. · · 2024 · cited 265× · PMID 39294640 · DOI 10.1186/s12943-024-02119-3
5. Molecular remission and response patterns in patients with mutant-<i>IDH2</i> acute myeloid leukemia treated with enasidenib.
   Stein EM, DiNardo CD, Fathi AT, Pollyea DA, et al · · 2019 · cited 242× · PMID 30510081 · DOI 10.1182/blood-2018-08-869008
6. Mutations in AML: prognostic and therapeutic implications.
   DiNardo CD, Cortes JE. · · 2016 · cited 198× · PMID 27913501 · DOI 10.1182/asheducation-2016.1.348
7. ROS homeostasis and metabolism: a critical liaison for cancer therapy.
   Kim J, Kim J, Bae JS. · · 2016 · cited 183× · PMID 27811934 · DOI 10.1038/emm.2016.119
8. Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics.
   Golub D, Iyengar N, Dogra S, Wong T, et al · · 2019 · cited 176× · PMID 31165048 · DOI 10.3389/fonc.2019.00417