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Leukemia, Myeloid, AcutePhase 2NCT04522895

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

A Phase 2 study testing Enasidenib in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Heinrich-Heine University, Duesseldorf at 11 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Enasidenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
11 sitesGermany
Study dates
27 Aug 2020to 24 Jul 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.
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  • 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
  • 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)

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites

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

    Aachen, 52074

  • Universitätsklinikum Köln Klinik I für Innere Medizin

    Cologne, 50937

  • Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik I

    Dresden, 01307

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

    Düsseldorf, North Rhine-Westphalia, 40225

  • Universitätsklinikum Essen Klinik für Hämatologie und Stammzelltransplantation

    Essen, 45147

  • Universitätsklinikum Frankfurt Med. Klinik II

    Frankfurt, 60590

  • Universitätsklinikum Hamburg-Eppendorf Interdisziplinäre Klinik für Stammzelltransplantation

    Hamburg, 20246

  • Universitätsklinikum Heidelberg Innere Medizin V: Hämatologie, Onkologie und Rheumatologie

    Heidelberg, 69120

  • Universitätsklinikum Leipzig Medizinische Klinik und Poliklinik I, Hämatologie und Zelltherapie

    Leipzig, 04103

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

    München, 81675

  • Universitätsklinikum Münster Medizinische Klinik A / KMT Zentrum

    Münster, 48149

Other trials in Germany

About this study

Official title: IDH2-Post-Allo-Trial: Enasidenib As Consolidation or Salvage Therapy for Patients with IDH2 Mutated AML or MDS Following Allogeneic Blood Stem Cell Transplantation

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.

Read the detailed description

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.

Study Design:

  • interventional
  • prospective, open-label, single arm, multicenter phase-II trial
  • total patients sample size: 50 patients
  • number of trial sites: 11 all located in Germany and members of the EBMT

Patients with AML, MDS and CMML, in whom an IDH2 mutation has been detected at diagnosis prior allo-SCT, are eligible for consolidation therapy, if they are in complete hematological remission after first allo-SCT. IDH2 mutation might be absent at this time (CRMRDnegative), or might be detectable at submicroscopical levels (CRMRDpositive) given the high sensitivity of detection methods nowadays available. Remission will be evaluated within a screening period between day +25 and day +35. Evaluation of remission will be performed locally with IDH2 mutation analysis performed at an experienced local laboratory of the respective center. The report about IDH2 mutation testing at diagnosis has to be sent to the principle investigator for review at screening to include the patient; a BM sample will be stored for central retesting, which will be performed in batch during the course of the study. Having a documented hematological CR, patients will enter the treatment phase within 30 days after this BM evaluation (latest time point day +65) and start treatment with Enasidenib. They are envisaged to receive Enasidenib (100 mg per day, day 1-28) for up to 12 cycles (=12 months). Patients will go off protocol prematurely in case of relapse, intolerability of study treatment and in case of withdrawal of consent. In those patients who relapse during study treatment subsequent therapy for relapse will be performed according to the choice of the individual treating physician. Patients who finish study as planned or prematurely will be regularly followed for one year, lost to follow up, death or withdrawal of consent.

Being tested
Enasidenib
Keywords
IDH2 Gene Mutation, MDS, CMML, AML, allogeneic blood stem cell transplantation, maintenance, consolidation
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnasidenibDrug

    Participants receive up to 12 cycles of Enasidenib.

Study groups in NCT04522895
Study groupRoleWhat they receive
Consolidation ArmExperimentalEnasidenib (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.
Receives: Drug: Enasidenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: through study completion, an average of 2 years

Secondary outcomes (13)

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

    Number of participants who maintain Remission (molecular/hematological) as a measure of efficacy

    Measured: through study completion, an average of 2 years

  2. Overall Survival

    Days from start of Treatment and from date of allo-SCT until death or last follow up as a measure of efficacy

    Measured: through study completion, an average of 2 years

  3. Relapse-free Survival

    Days from evaluation of remission at screening and from date of allo-SCT until relapse, death, or last follow up as a measure of efficacy

    Measured: through study completion, an average of 2 years

  4. Non-relapse mortality

    Days from evaluation of remission at screening and from date of allo-SCT until death without relapse or last follow up as a measure of efficacy

    Measured: through study completion, an average of 2 years

  5. Relapse incidence

    number of participants that relapse during the study as a measure of efficacy

    Measured: through study completion, an average of 2 years

  6. Numbers of Participants Meeting Criteria of Treatment Failure

    Number of participants who require any cellular or pharmacological intervention due to pending or frank relapse (defined as treatment-failure) as a measure of efficacy

    Measured: through study completion, an average of 2 years

  7. Correlation of cytogenetics/molecular alterations and relapse-free survival

    Comparison of relapse-free survival between different cytogenetics/molecular subtypes as a measure of efficacy using time to event curves and log-rank test

    Measured: through study completion, an average of 2 years

  8. Incidence, course and severity of aGvHD and cGvHD

    Incidence, course and severity of aGvHD and cGvHD as a measure of safety

    Measured: through study completion, an average of 2 years

  9. Number of hospitalizations

    Number of hospitalizations per participant as a measure of safety

    Measured: through treatment completion, an average of 1 year

  10. Number of participants who require dose reductions for toxicity reasons

    Number of participants who require dose reductions for toxicity reasons as a measure of safety

    Measured: through treatment completion, an average of 1 year

  11. Number of participants who have to stop consolidation therapy due to toxicity (Consolidation Arm)

    Number of participants who have to stop consolidation therapy due to toxicity as a measure of safety (Consolidation Arm)

    Measured: through treatment completion, an average of 1 year

  12. Number of participants who can receive all 12 cycles of consolidation therapy(Consolidation Arm)

    Number of participants who can receive all 12 cycles of consolidation therapy as a measure of Safety (Consolidation Arm)

    Measured: through treatment completion, an average of 1 year

  13. Number of screened participants that can start consolidation therapy within the envisaged time frame (Consolidation Arm)

    Number of screened participants that can start consolidation therapy within the envisaged time Frame as a measure of safety (Consolidation Arm)

    Measured: up to 65 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2020
  2. Study start27 Aug 2020
  3. Primary completion24 Jul 2024
  4. Study completion24 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
single arm
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04522895
Sponsor's protocol ID
AG-221CL-AML-PI13299
Other IDs
2019-001416-30, 2019
Status last verified
Dec 2023
First submitted
29 May 2020
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enasidenib in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Heinrich-Heine University, Duesseldorf at 11 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Type, incidence and severity of adverse events specifying seriousness and expectedness (AE, SAE, SUSAR) (time frame: through study completion, an average of 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04522895.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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