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

NCT04522895 | Completed Phase 2 DMC

• 2 other identifiers: AG-221CL-AML-PI132992019-001416-30
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 11

Brief Summary

This is a prospective, open label, single arm, multi-centre phase II trial 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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; IDH2 Gene Mutation; IDH2 R172; IDH2 R140

Keywords

IDH2 Gene Mutation; MDS; CMML; AML; allogeneic blood stem cell transplantation; maintenance; consolidation

Outcome Measures

Primary Outcomes (1)

• Type, incidence and severity of adverse events specifying seriousness and expectedness (AE, SAE, SUSAR)

  Number of participants with Adverse Events as assessed by CTCAE v5.0

  through study completion, an average of 2 years

Secondary Outcomes (13)

• Number of participants who maintain remission (molecular/hematological) after allo-SCT

  through study completion, an average of 2 years

• Overall Survival

  through study completion, an average of 2 years

• Relapse-free Survival

  through study completion, an average of 2 years

• Non-relapse mortality

  through study completion, an average of 2 years

• Relapse incidence

  through study completion, an average of 2 years

Study Arms (1)

Consolidation Arm

EXPERIMENTAL

Enasidenib (investigational product) will be started on day 1 for 28 days every 28 days for a maximum of 12 cycles. The starting dose of Enasidenib will be 100 mg once daily in every patient and may be reduced individually according to a dose modification scheme.

Drug: Enasidenib

Interventions

Enasidenib DRUG

Participants receive up to 12 cycles of Enasidenib.

Consolidation Arm

Eligibility Criteria

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

You may qualify if:

• 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 (the hematological remission will be confirmed locally by cytomorphological/histological evaluation)
• 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
• no previous therapy with Enasidenib or any other IDH2 inhibitor
• ECOG performance status ≤ 2 at study entry (s. Appendix)
• 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

You may not qualify if:

• 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 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 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 active infectious hepatitis, type A, B or C

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• Celgene Corporation: collaborator
• Koordinierungszentrum für Klinische Studien Düsseldorf: collaborator

Study Sites (11)

University Hospital Duesseldorf Dept. of Hematology, Oncology and Clinical Immunology

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Uniklinik RWTH Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation (Med. Klinik IV)

Aachen, 52074, Germany

Location

Universitätsklinikum Köln Klinik I für Innere Medizin

Cologne, 50937, Germany

Location

Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik I

Dresden, 01307, Germany

Location

Universitätsklinikum Essen Klinik für Hämatologie und Stammzelltransplantation

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt Med. Klinik II

Frankfurt, 60590, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Interdisziplinäre Klinik für Stammzelltransplantation

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg Innere Medizin V: Hämatologie, Onkologie und Rheumatologie

Heidelberg, 69120, Germany

Location

Universitätsklinikum Leipzig Medizinische Klinik und Poliklinik I, Hämatologie und Zelltherapie

Leipzig, 04103, Germany

Location

Klinikum rechts der Isar der TU München Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie

München, 81675, Germany

Location

Universitätsklinikum Münster Medizinische Klinik A / KMT Zentrum

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

enasidenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas Schroeder, PD Dr.

  University Hospital Duesseldorf Dept. of Hematology, Oncology and Clinical Immunology

  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

Model Details: single arm

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: August 21, 2020
• Study Start: August 27, 2020
• Primary Completion: July 24, 2024
• Study Completion: July 24, 2024
• Last Updated: September 19, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11)