IDH2-Post-Allo-Trial for Patients With IDH2-mut Myeloid Neoplasms After Allo-SCT

• Status: Recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, open label, multi-centre phase II trial with a two-arm non comparative design aiming to evaluate the safety and efficacy of Enasidenib (investigational product) as prophylactic consolidation in patients with IDH2-mutated MDS, CMML and AML in remission after allo-SCT and as salvage therapy in patients with IDH2-mutated MDS, CMML and AML who have relapsed after allo-SCT.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: Celgene Corporation; Koordinierungszentrum für Klinische Studien Düsseldorf

Criteria

Inclusion Criteria:

Consolidation Arm:

• Patients with myeloid malignancy (AML, MDS and CMML) and known IDH2 mutation (IDH2 R172 or R140 mutation) at diagnosis prior to first allo-SCT

• molecular CR after allo-SCT determined during screening period between day +25 and day +35 (detected by the local laboratory of the respective center, the report has to be sent to the principle investigator for review at screening to include the patient; a sample will be stored for central retesting, which will be performed in batch during the course of the study)

• Hematopoietic recovery after transplantation indicated by an absolute neutrophil count of at least 1.000/µl and platelet count of at least 50.000/µl

Salvage Arm:

• First hematological or molecular relapse (reoccurrence or persistence of IDH2 mutation) of de novo or therapy related AML, MDS or CMML according to WHO 2016 classification after first allo-SCT (HLA-identical related or matched unrelated donor [≥9/10], haploidentical donor)

• IDH2 R172 or R140 mutation at the time of relapse after allo-SCT (detected by the local laboratory of the respective center, the report has to be sent to the principle investigator for review at screening to include the patient; a sample will be stored for central retesting, which will be performed in batch during the course of the study)

• Possibility of DLI (no cord blood)

• no previous therapy for relapse after allo-SCT except for hydroxyurea for a maximum of 14 days during screening phase prior start of study medication

Both Arms:

• no previous therapy with Enasidenib or any other IDH2 inhibitor

• ECOG performance status ≤ 2 at study entry (s. Appendix)

• no active, steroid refractory GvHD treated with additional systemic immunosuppression within 4 weeks before inclusion

• no uncontrolled infection at inclusion

• Understand and voluntarily sign an informed consent form.

• Age ≥18 years at the time of signing the informed consent form.

• Able to adhere to the study visit schedule and other protocol requirements.

• Female of childbearing potential (FCBP) must:

Understand that Enasidenib can cause embryo-fetal harm when administered to a pregnant woman Agree to have a medically supervised pregnancy test within 72 hours prior study start and at day 1 of every treatment cycle Use effective contraception during treatment with Enasidenib and for at least 2 months after the last dose Coadministration of Enasidenib may increase or decrease the concentrations of combined hormonal contraceptives Avoid becoming pregnant while receiving Enasidenib Notify her study doctor immediately if there is a risk of pregnancy Agree to abstain from breastfeeding during study participation and for at least 30 days after study drug discontinuation Understand that Enasidenib may impair fertility in females of reproductive potential and this effect may be not reversible

• Males must: Understand that Enasidenib can cause embryo-fetal harm Use effective contraception during treatment with Enasidenib and for at least 2 months after the last dose of Enasidenib if engaged in sexual activity with a pregnant female or a female with childbearing potential Agree to notify the investigator immediately, if pregnancy or a positive pregnancy test occurs in his partner during study participation Understand that Enasidenib may impair fertility in males of reproductive potential and this effect may be not reversible

Exclusion Criteria:

Consolidation Arm:

• Any evidence of activity of the underlying IDH2-mutated myeloid malignancy (AML, MDS and CMML) determined during screening period until start of treatment

• Any previous prophylactic therapy given within the interval between allo-SCT and screening period

• Patients with myeloid malignancy (AML, MDS and CMML) and known IDH2 mutation (IDH2 R172 or R140 mutation) after second allo-SCT

Salvage Arm:

• No IDH2 R172 or R140 mutation at the time of relapse

• Relapse after second allogeneic transplantation

• Any previous therapy (chemotherapy, radiation or investigational drugs) administered as therapy for relapse after allo-SCT except for hydroxyurea for a maximum of 14 days during screening phase prior start of study medication

• Non-infectious leukocytosis (WBC > 30x10^9/L)

Both Arms:

• previous transplantation with cord blood

• Active, steroid refractory GvHD treated with additional systemic immunosuppression within the last 4 weeks

• Uncontrolled infection

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Pregnant or lactating females

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Impaired renal function (GFR < 30 ml/min)

• Impaired hepatic function, as follows:

Aspartate aminotransferase (19) ≥3 x ULN or Alanine aminotransferase (ALT) ≥3 x ULN or Total bilirubin ≥3 x ULN Alkaline Phosphatase ≥3 x ULN

• Known hypersensitivity to Enasidenib or any other component of the treatment

• Prior history of malignancy other than AML, MDS or CMML (except basal and squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥3 years

• Concurrent use of other anti-cancer agents or treatments

• Known positive for HIV or active infectious hepatitis, type A, B or C

• Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment until the end of the study (in cases where the investigational product has an unusually long half-life (e.g. antibodies), the interval until study enrollment must be at least five times the plasma half-life of the investigational product)