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Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients

ConditionAcute Myeloid Leukemia With Gene Mutations
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorPETHEMA Foundation

About this trial

The goal of this clinical trial is to learn if the combination of oral decitabine plus ivosidenib works to treat naïve adult patients with acute myeloid leukemia (AML) with IDH1 R132 mutation older than 60 years old or those who are older than 18 years old with defined comorbidities that make them not suitable for standard induction therapy. The main objectives of this clinical trial are:

* Asses the Complete Remission (CR) and Complete Remission with incomplete marrow recovery (CRi) rates of this treatment. * Determine the incidence and severity of all adverse events (AEs).

All participants will receive oral ivosidenib and oral decitabine in treatment cycles of 28 days until disease progression, lack of clinical benefit or the end of the study. Patients who achieve CR/CRi will be elegible to receive allogeneic stem cell transplantation.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Morphological diagnosis of AML (WHO criteria 2022)

Newly diagnosed AML.

IDH1 R132 mutations (centrally assessed by PCR and NGS). A patient will be allowed to be included with local result after approval of the medical monitor.

Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2 if ≥ 60 years of age, or 0 to 3 if ≥ 18 to 60 years.

Disqualifiers

Subject has history of myeloproliferative neoplasm [MPN] with BCR-ABL1 translocation and AML with BCR-ABL1 translocation.

Prior therapy for AML (except hydroxiurea).

Genetic diagnosis of acute promyelocytic leukemia.

Subject is known to be positive for HIV (HIV testing is not required.)

Trial design

Design model

Single group

Treatments tested in this trial

  • Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLET

    Drug

    Oral Decitabine (Decitabine/Cedazuridine 35 Mg-100 Mg) will be administerd on Days 1-5 of each treatment cycle

  • Ivosidenib Oral Tablet

    Drug

    Ivosidenib 500 mg/orally on Days 1-28 of each treatment cycle

  • Hydroxyurea

    Drug

    0.5-6 gram/day orally during the screening period and the two first treatment cycles if hyperleukocytosis at diagnosis

  • Cytarabine

    Drug

    Maximum 1 gram/sqm/day during the screening period and the two first treatment cycles if hyperleukocytosis at diagnosis

  • Allogeneic stem cell transplantation

    Procedure/Surgery

    Only for those participants achieving CR/CRi

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Decitabine+IvosidenibExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Rate of CR/CRi

To assess the rates of Complete Remission (CR) and Complete Remission with incomplete marrow recovery (CRi) of participants treated with Ivosidenib plus Decitabine

Time frame
3 years

Secondary outcomes

1

Rate CR/CRi compared to historical cohort

To evaluate the CR (Complete Remission)/CRi (Complete Remission with incomplete marrow recovery) rates after 2, 3 and 6 cycles of Ivosidenib and oral Decitabine, and compare with a matched historical cohort.

Time frame
3 years
2

OS compared to historical cohort

To assess OS (overall survival, measured as the number of days from the date of enrollment to the date of death, whatever the cause of death) and compare the median between Ivosidenib with oral Decitabine and a matched historical cohort.

Time frame
3 years
3

EFS compared to historical cohort

To evaluate EFS (event-free survival, defined as the number of days from enrollment until the date of progressive disease, relapse from CR or CRi, failure to achieve CR or CRi, or death from any cause) and compare with a matched historical control cohort

Time frame
3 years
4

Hematologic and non-hematologic toxicity and AE

Toxicity and adverse events (AE) will be recorded and evaluated to determine treatment safety. Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.019.

Time frame
3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

PETHEMA Foundation

Lead sponsor

Source ClinicalTrials.gov
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