IDH2 (AG 221) Inhibitor in Patients With IDH2 Mutated Myelodysplastic Syndrome

NCT03744390 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: GFM-IDEAL Study
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 22

Brief Summary

patients with MDS (Myelodysplastic Syndrome) and mutated IDH2 patients will be treated with AG221 (IDH2 inhibitor)

Conditions

Myelodysplastic Syndromes; Leukemia Acute Myeloid

Outcome Measures

Primary Outcomes (1)

• Overall hematological response

  Overall hematological response

  6 months

Secondary Outcomes (2)

• Duration Response

  3 years

• Progression IPSS

  3 years

Study Arms (1)

AG-221

EXPERIMENTAL

Subjects enrolled will receive continuous 28-day cycles of AG-221 - 100 mg.

Drug: AG-221

Interventions

AG-221 DRUG

Subjects enrolled will receive continuous 28-day cycles of AG-221 -100 mg.

Also known as: Enasidenib

AG-221

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to participate in the study:
• Myelodysplastic syndrome according to World Health Organization (WHO) classification including non-proliferative AML up to 29% of Bone marrow (BM) blast
• Age ≥ 18 years
• Belonging to one of the following categories:
• higher risk MDS (IPSS int-2, high) without response to azacitidine (Complete response (CR),Partial Response (PR), stable disease with HI) after at least 6 cycles , or relapsing after a response but without overt progression (defined by at least doubling of marrow blasts, compared to pre azacitidine bone marrow, or AML progression beyond 30% blasts)
• Untreated higher risk MDS (IPSS int-2, high) without life threatening cytopenia including absolute neutrophil count (ANC) \<500/mm3 or any recent severe infections and/or platelets below 30,000/mm3 and any bleeding symptom
• Lower risk MDS with resistance or loss of response to a previous treatment with epoetin alpha/ beta (≥60000 U/w) or Darbopoetin (≥250 ug/w) given for at least 12 weeks and red blood cell (RBC) transfusion requirement at least 2 U/8 weeks in the previous 16 weeks.
• Presence of IDH2 mutation in either blood or marrow prior to start of therapy
• Normal renal function, defined by creatinine less than 1.5 times the upper limit of normal, creatinine clearance (Modification of diet in renal disease) (MDRD) ≥ 50 mL/min.
• Normal liver function, defined by total bilirubin and transaminases less than 1.5 times the upper limit of normal.
• Adequate cardiac ejection fraction (\>40%)
• Patient is not known to be refractory to platelet transfusions.Written informed consent.
• Patient must understand and voluntarily sign consent form.
• Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at the time of screening.

You may not qualify if:

• A patient meeting any of the following criteria is not eligible to participate in the study:
• Severe infection or any other uncontrolled severe condition.
• Significant cardiac disease - New York Heart Association (NYHA) Class III or IV or having suffered a myocardial infarction in the last 6 months.
• Less than 14 days since prior treatment with growth factors (EPO, G-CSF).
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before the study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicity from any previous therapy.
• Subject has a heart-rate corrected QT interval using Fridericia's method (QTcF) ≥ 470 msec or any other factor that increases the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with prolonged QTcF interval in the setting of bundle branch block may participate in the study.
• Active cancer or cancer during the year prior to trial entry other than basal cell carcinoma, or carcinoma in situ of the cervix or breast.
• Patient already enrolled in another therapeutic trial of an investigational drug.
• Known HIV infection or active hepatitis B or C.
• Women who are or could become pregnant or who are currently breastfeeding.
• Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form.
• Patient eligible for allogeneic stem cell transplantation.
• Known allergies to AG-221 or any of its excipients.
• No affiliation to a health insurance system.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead

Study Sites (22)

Hôpital André Mignot

Versailles, LE Chesnay, 78157, France

Location

CHU Montpellier St Eloi

Montpellier, Montpellier, 34295, France

Location

CH d'Angers/Service des Maladies du sang

Angers, 49933, France

Location

centre hospitalier Victor Dupouy

Argenteuil, 95107, France

Location

CH de la Cote Basque

Bayonne, 64109, France

Location

CHU de Bordeaux

Bordeaux, 33604, France

Location

CHU Côte de Nacre/Service d'Hématologie Clinique

Caen, 14033, France

Location

Hôpital Henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CH Le Mans/Service d'hématologie Oncologie

Le Mans, 72000, France

Location

CH lyon

Lyon, 69495, France

Location

Institut Paoli Calmettes/Unité d'Hématologie 3

Marseille, 13009, France

Location

GHR Mulhouse Sud-Alsace

Mulhouse, 68100, France

Location

CHU Nantes - Hôtel Dieu/Service d'Hématologie Clinique

Nantes, 44093, France

Location

Hôpital Archet 1/Service d'Hématologie Clinique

Nice, 06202, France

Location

CHU de Nimes

Nîmes, 30029, France

Location

Hôpital Saint Louis - Service d'hématologie séniors

Paris, 75010, France

Location

Hôpital saint Antoine

Paris, 75571, France

Location

Centre Henri Becquerel/Département d'Hématologie

Rouen, 76 038, France

Location

Institut de cancérologie Lucien Neuwirth Saint priest en Jarez

Saint-Priest-en-Jarez, 42271, France

Location

Médecine Interne/IUCT Oncopole

Toulouse, 31059, France

Location

CHU de Tours

Tours, 37044, France

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

enasidenib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Lionel ADES, Pr

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 16, 2018
• Study Start: April 2, 2019
• Primary Completion: February 18, 2023
• Study Completion: March 18, 2026
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (22)