Prospective Evaluation of Ivosidenib Maintenance Following Allogeneic Stem Cell Transplantation (alloSCT) In Patients with Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Neoplasia (HR-MDS) with IDH1 Mutation (PIVOT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Technische Universitat Dresden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jun 2025 → ongoing

Decision date (initial)

2025-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Servier (Servier Affaires Médicales and Servier Deutschland GmbH)

External identifiers

EU CT number

2023-509055-14-00

ClinicalTrials.gov

NCT06717958

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Main objective it to evaluate the efficacy of Ivosidenib (investigational drug) to improve event-free survival in patients with AML or MDS carrying an IDH1 mutation when given as 24 months maintenance therapy following allo SCT.

Secondary objectives 3

1. Efficacy of Ivosidenib maintenance therapy measured by overall survival
2. Determination of effect of Ivosidenib maintenance therapy on measureable residual disease (MRD) levels
3. Determination of effect of Ivosidenib maintenance therapy on frequency and severity of GvHD

Conditions and MedDRA coding

myelodysplastic neoplasia (MDS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age ≥ 18 years
2. Informed consent signed by the patient capable of giving
3. Eastern Cooperative Group (ECOG) performance status ≤
4. AML or MDS according to WHO criteria with IDH1 mutation
5. having received alloSCT within the past 100 days
6. documented CR, CRi, CRh or MLFS after alloSCT within 28 days prior to enrolment (documented by bone marrow aspiration)
7. Adequate organ function defined by: Serum creatinine clearance > 30 mL/min; calculated by the Cockcroft Gault formula
8. Adequate organ function defined by: Serum total bilirubin ≤2 × ULN, unless considered to be due to Gilbert’s disease
9. Adequate organ function defined by: Left ventricular ejection fraction (LVEF) ≥ 35%
10. Negative serum pregnancy test
11. Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 1 month after the last dose of the investigational medicinal product
12. Willingness and ability to comply with all study procedures

Exclusion criteria 20

1. Active acute GvHD grade III-IV according to Harris criteria requiring steroids > 1 mg/kg prednisolone equivalent
2. Hypersensitivity known from medical history to Ivosidenib or its ingredients or to drugs with a similar chemical structure
3. Having received any unlicensed drug within 30 days or 5 half-lives, whichever is greater, prior to enrolment
4. Addictions or other illnesses that do not allow the patient concerned to assess the nature and extent of the clinical trial and its possible consequences
5. Pregnant or breastfeeding women, breastfeeding has to be discontinued before onset of treatment and until for at least 1 month after the last dose
6. Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: post-menopausal (12 months natural amenorrhoea or 6 months amenorrhoea with serum FSH > 40 U/ml)
7. Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: postoperative (6 weeks after bilateral ovariectomy with or without hysterectomy)
8. Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: medically confirmed ovarian failure
9. Patients who are unwilling to follow strictly highly effective contraception requirements including hormonal contraceptives with a Pearl Index < 1% per year in combination with a barrier method from time point of signing the informed consent until 1 month after the last dose of the IMP unless one of the following criteria is met: vasectomy of the partner
10. Indications that the subject is unlikely to adhere to the protocol (e.g., lack of compliance)
11. Substance abuse, medical, psychological, or social conditions that may interfere with the subject’s cooperation with the requirements of the trial or evaluation of the study results
12. Significant cardiac disease: i.e., heart failure NYHA III or IV; unstable angina pectoris; recent myocardial infarction or clinically significant bradycardia
13. Long QT syndrome (QTcF ≥480 msec on screening ECG)
14. Concurrent use of medications that have a relative risk of prolonging QT interval or of inducing Torsade de Pointes unless it is secured that if patient receive medications with known QT interval prolonging potential concomitantly, ECG monitoring has to be conducted weekly, or more frequently based on institutional standards or investigator discretion for the first 3 weeks following initiation of Ivosidenib treatment
15. Pulmonary disease with clinically relevant hypoxia (need for oxygen inhalation)
16. Patients undergoing renal dialysis
17. Active severe or uncontrolled infection
18. Any condition that limits the ingestion or gastrointestinal absorption of orally administered drugs
19. Diagnosis of another primary malignancy that is currently clinically significant or currently requires active treatment / intervention
20. Concomitant administration of dabigatran and/or a familial history of sudden death or polymorphic ventricular arrhythmia and/or the rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of event-free survival (EFS) at two years after study inclusion. Events are defined as death from any cause or disease relapse defined as reappearance of leukemic blasts in peripheral blood or ≥ 5% bone marrow blasts or development of extramedullary disease as defined according to 1 or end of or initiation of any new anti-cancer therapy.

Secondary endpoints 10

1. Rate of overall survival (OS) at two years after study inclusion (written informed consent).
2. EFS and OS as time-to-event analysis including follow-up.
3. Rate of complete molecular remissions (CRMRD-) as defined by international consensus guidelines at 6, 12 and 24 months after study inclusion.
4. MRD conversion rate from positive (CRMRD+) to negative (CRMRD−) as defined by international consensus guidelines among subjects with measurable residual disease at baseline.
5. Cumulative incidence of higher grade acute GvHD defined as new onset of or increase in severity to grade III-IV aGVHD as defined by investigator following international expert consensus guidelines .
6. Cumulative incidence and maximal grade (according to international expert consensus guidelines) of chronic GvHD requiring systemic treatment within one year after alloSCT.
7. Cumulative incidence of AEs/SAEs Grade ≥3 or leading to dose reduction/discontinuation of study treatment.
8. Cumulative incidences of non-relapse mortality within 100 days and 2 years from study inclusion defined as death that was not proceeded by recurrent or progressive malignancy.
9. Cumulative incidence of relapse mortality within 2 years from study inclusion.
10. Number of patients who require dose reductions or have to stop study treatment due to toxicity reasons.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Technische Universitat Dresden

Sponsor organisation

Technische Universitat Dresden

Address

Mommsenstrasse 11, Raecknitz/zschertnitz Raecknitz/zschertnitz

City

Dresden

Postcode

01069

Country

Germany

Scientific contact point

Organisation

Technische Universitat Dresden

Contact name

Dr. med. Jan Moritz Middeke

Public contact point

Organisation

Technische Universitat Dresden

Contact name

Dr. med. Jan Moritz Middeke

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications