IDH1 (AG 120) Inhibitor in Patients With IDH1 Mutated Myelodysplastic Syndrome
A Single-arm Phase II Multicenter Study of IDH1 (AG 120) Inhibitor in Patients With IDH1 Mutated Myelodysplastic Syndrome
1 other identifier
interventional
68
2 countries
38
Brief Summary
patients with MDS (Myelodysplastic Syndrome) and mutated IDH1 patients will be treated with AG120 (IDH1 inhibitor)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2019
Longer than P75 for phase_2
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 4, 2018
CompletedFirst Posted
Study publicly available on registry
April 19, 2018
CompletedStudy Start
First participant enrolled
May 14, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 2, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 2, 2027
May 18, 2025
May 1, 2025
7.9 years
April 4, 2018
May 16, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Overall hematological response
overall hematological response
6 months
Secondary Outcomes (2)
response duration
3 years
IPSS progression
3 years
Study Arms (1)
AG-120
EXPERIMENTALSubjects enrolled will receive continuous 28-day cycles of AG-120 - 500 mg. AG-120 will be dispensed on Day 1 of each treatment cycle
Interventions
500 mg/day Oral of AG-120. AG-120 will be dispensed on Day 1 of each treatment cycle
Eligibility Criteria
You may qualify if:
- Patients must meet all of the following criteria to participate in the study:
- Age ≥ 18 years
- Myelodysplastic syndrome according to WHO classification including non-proliferative AML up to 29% of BM blast
- Belonging to one of the following categories :
- higher risk (IPSS high or int 2 ) MDS without response to azacitidine (CR,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 ANC \<500/mm3 or any recent severe infections and /or platelets below 30,000/mm3 or 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 RBC transfusion requirement at least 2 U/8 weeks in the previous 16 weeks
- Presence of IDH1 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) creatinine clearance ≥ 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;
- +5 more criteria
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 - 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.
- Subject is taking known strong cytochrome P450 (CYP) 3A4 inducers or inhibitors or sensitive CYP3A4 substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
- Subject is taking P-glycoprotein (P-gp) transporter-sensitive substrate medications with a narrow therapeutic window, unless they can be transferred to other medications within ≥ 5 half-lives prior to administration of study treatment
- 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 120 or any of its excipients.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (38)
CH Angers
Angers, 49933, France
Centre Hospitalier de la Côte Basque
Bayonne, 64109, France
Hôpital Nord Franche-Comté/Service de médecine interne / Hématologie clinique
Belfort, 90015, France
CHU côte de Nacre
Caen, 14033, France
CHU de Grenoble/Clinique Universitaire d'hématologie 6e A
Grenoble, 38043, France
CH Le Mans/Service d'hématologie Oncologie
Le Mans, 72000, France
CHRU de Limoges
Limoges, 87046, France
centre hospitalier de Lyon
Lyon, 69495, France
Institut Paoli Calmettes/Unité d'Hématologie 3
Marseille, 13273, France
CHU Montpellier St Eloi
Montpellier, 34295, France
Hôpital E. Muller-GHR Mulhouse Sud-Alsace
Mulhouse, 68100, France
CHU Hôtel Dieu/Service d'Hématologie Clinique
Nantes, 44093, France
Hôpital Archet 1/Service d'Hématologie Clinique
Nice, 06200, France
GHU Caremeau
Nîmes, 30029, France
Hôpital Saint Louis - Hématologie Séniors
Paris, 75010, France
Hôpital Necker
Paris, 75743, France
Hôpital Henri Mondor
Paris, 94010, France
CHU de Haut-Lévèque/Centre François Magendie/Service des maladies du sang
Pessac, 33604, France
CHU de Poitiers/Pôle de cancérologie - secteur tertiaire-
Poitiers, 86021, France
Centre Henri Becquerel
Rouen, 76038, France
institut de cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez, 42271, France
Médecine Interne/IUCT Oncopole
Toulouse, 31059, France
CHU de Tours
Tours, 37044, France
CHU Brabois
Vandœuvre-lès-Nancy, 54511, France
Centre Hospitalier de Versailles-Hôpital André Mignot
Versailles, 78157, France
Ematologia ALESSANDRIA
Alessandria, 16115121, Italy
CLINICA Ematologica ANCONA
Ancona, 7160126, Italy
Ematologia BOLOGNA
Bologna, 40138, Italy
Ematologia BRESCIA
Brescia, 125123, Italy
Ematologia FIRENZE
Florence, 350134, Italy
Clinica Ematologica Genova
Genova, 1016132, Italy
Ematologia GENOVA
Genova, 1016132, Italy
Ematologia LECCE
Lecce, 73100, Italy
Ematologia MILANO
Milan, 3520122, Italy
Ematologia ORBASSANO
Orbassano, 1010043, Italy
Ematologia ed Immunologia Clinica PADOVA
Padua, 235128, Italy
Reggio Calabria
Reggio Calabria, 2189124, Italy
Ematologia ROMA
Roma, 1000144, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marie Sébert, Dr
APHP
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
April 4, 2018
First Posted
April 19, 2018
Study Start
May 14, 2019
Primary Completion (Estimated)
April 2, 2027
Study Completion (Estimated)
April 2, 2027
Last Updated
May 18, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share