Patients with myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) or acute myelogenous leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) and with an IDH2 mutation (IDH2 R172 or R140 mutation) MedDRA version: 20.1 Level: LLT Classification code 10024329 Term: Leukemia System Organ Class: 100000004864
Conditions
Sponsors
Heinrich-Heine-University Düsseldorf represented by the Coordinating Investigator
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with myeloid malignancy (AML, MDS and CMML) and known IDH2 mutation (IDH2 R172 or R140 mutation) at diagnosis prior to first allo-SCT • hematological CR after allo-SCT determined during screening period between day+25 and day +35 • Hematopoietic recovery after transplantation indicated by an absolute neutrophil count of at least 1.000/microliter and platelet count of at least 50.000/microliter • 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 prior to starting of Enasidenib • 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: • Any evidence of hematological relapse 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 • Active, steroid refractory GvHD treated with additional requiring 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:primar Aspartate aminotransferase =3 x ULN or Alanine aminotransferase (ALT) =3 x ULN or Total bilirubin =3 x ULN or 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 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and feasibility of Enasidenib (investigational drug) as 12 months consolidation therapy after allo-SCT in patients with myeloid malignancies (AML, MDS and CMML) carrying an IDH2 R172 or R140 Mutation ;Secondary Objective: To descriptively assess the efficacy of Enasidenib (investigational drug) as 12 months consolidation therapy after allo-SCT in patients with myeloid malignancies (AML, MDS and CMML) carrying an IDH2 R172 or R140 Mutation;Primary end point(s): • To evaluate the safety and feasibility of Enasidenib (investigational drug) as 12 months consolidation therapy after allo-SCT in patients with myeloid malignancies (AML, MDS and CMML) carrying an IDH2 R172 or R140 Mutation ;Timepoint(s) of evaluation of this end point: 1. Annual Review of Safety Data by DMC, based on DSUR data 2. Interim Analysis (as 10 patients will have been treated within each arm and the 10th patient in each arm has either completed 4 cycles or has discontinued treatment whichever occurs first. In case one of the two arms is recruiting significantly slower than the other arm, an independent interim analysis of the individual arms may be performed optionally.) 3. End of Study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy variables: • Number of patients who maintain remission (molecular/hematological) after allo-SCT • Overall survival • Relapse-free survival • Non-relapse mortality • Relapse incidence • Number of patients who require any cellular or pharmacological intervention due to pending or frank relapse (defined as treatment-failure) • Correlation of relapse-free survival and cytogenetics/molecular alterations Safety variables: • Incidence, course and severity of aGvHD and cGvHD • Number of hospitalizations • Number of patients who require dose reductions due to toxicity reasons • Number of patients who have to stop consolidation therapy due to toxicity • Number of patients who can receive all 12 cycles of consolidation therapy • Number of screened patients that can start consolidation therapy within the envisaged time frame ;Timepoint(s) of evaluation of this end point: 1. Annual Review of Safety Data by DMC, based on DSUR data 2. Interim Analysis (as 10 patients will have been treated within each arm and the 10th patient in each arm has either completed 4 cycles or has discontinued treatment whichever occurs first. In case one of the two arms is recruiting significantly slower than the other arm, an independent interim analysis of the individual arms may be performed optionally.) 3. End of Study | — |
Countries
Germany
Contacts
Public ContactCoordinating Investigator
University Hospital Düsseldorf, Dept. of Hematology, Oncology and Clinical Immunology
Outcome results
None listed