HOVON 177

A study to investigate the effect of adding revumenib to treatment with venetoclax + azacitidine in patients with acute myeloid leukemia (AML) with a specific gene abnormality who have not been previously treated and are not eligible for intensive chemotherapy

The treatment of patients with newly diagnosed AML for whom intensive chemotherapy is not an option continues to be an area of high unmet medical need. Combination therapy with two drugs, azacitidine and venetoclax, is the usual approach. Although this has led to significant advances in treatment, it has not resulted in a cure and may lead to relapses of the disease over time. The main objective of this study is to assess whether the addition of revumenib to treatment with azacitidine and venetoclax prolongs overall survival (OS) in adult patients with a mutation in the NPM1 or KMT2A gene and newly diagnosed AML who are not eligible for intensive chemotherapy. It is a randomized, double-blind, placebo-controlled clinical trial in which participants are treated until disease progression, the occurrence of side effects or death. A 4-year follow-up study will be conducted from the time of enrollment of the last patient to record the duration of survival and follow-up visits. Approximately 415 previously untreated patients with a mutation in the NPM1 or KMT2A gene and with newly diagnosed AML who are not eligible for intensive chemotherapy will participate in the study. Patients must be ≥ 18 years of age. Participants will be closely monitored for possible side effects of the study treatment. In the event of severe or too many side effects, the dosage of one or more drugs may be reduced or the dosage interrupted. The collection of additional blood and bone marrow does not represent any additional risk or discomfort for the study participants.

Intervention studied

The current study investigates whether the addition of revumenib to combination therapy improves the prognosis for AML patients with a mutation in the NPM1 or KMT2A gene.

The eligible patients are divided by lot into two equal groups. One group receives azacitidine/venetoclax with revumenib. The other group receives azacitidine/venetoclax with placebo (drug without active ingredients). Azacitidine is administered by injection (subcutaneously or intravenously). Venetoclax and revumenib or placebo will be administered as tablets. Patients are treated in 28-day cycles until disease progression, unacceptable toxicity or death.

During the study, most (diagnostic) procedures are part of the standard treatment. Please note that a maximum of 4 additional bone marrow examinations will be performed within 2 years and regular cardiac recordings will be made. If the bone marrow examination is performed according to the standard treatment, additional bone marrow (approximately 20 ml) will be collected for the study. If the blood collection is done according to the standard of care, additional blood will also be drawn. Patients will also be asked to complete quality of life questionnaires for the study.

Criteria for participation
The following can be included:

Patients with newly diagnosed NPM1-mutated AML, consistent with NPM1c, according to the 2022 International Consensus Classification (i.e. ≥ 10% blasts). OR patients with newly diagnosed BMT2A-rearranged AML according to the 2022 International Consensus Classification (i.e. ≥ 10% blasts).
Patients who are at least 18 years old (no upper age limit)
Patients who are not eligible for intensive induction chemotherapy

Exclusion criteria
The following cannot be included:

Patients who have previously been treated for AML
Patients with acute promyelocytic leukemia (APL)
Patients with significant active heart disease within 3 months prior to the start of study treatment
Patients with active infections that are uncontrolled prior to study treatment and could interfere with study objectives or could place the patient at undue risk by participating in the clinical trial; infections controlled with an approved antibiotic/antiviral/antifungal treatment that is not a strong or moderate CYP3A inducer are allowed.
Patients who have another current cancer
Patients who are pregnant, planning a pregnancy or breastfeeding

Further Studies: Leukemia

Recruitment completed

CLL 17

A prospective, randomized, unblinded, multicenter, phase III study comparing the efficacy and safety of ibrutinib monotherapy versus time-limited therapy with venetoclax plus obinutuzumab or ibrutinib plus venetoclax in patients with previously untreated chronic lymphocytic leukemia (CLL) - CLL17

Recruitment completed

HOVON 150

A multicenter, double-blind, randomized, placebo-controlled phase 3 study of ivosidenib or enasidenib in combination with induction therapy and consolidation therapy followed by maintenance therapy in patients with newly diagnosed acute myeloid leukemia or myelodysplastic syndrome with blast excess-2, with an IDH1 or IDH2 mutation, respectively, who are eligible for intensive chemotherapy.

Recruitment completed

HOVON 155

A randomized phase II multicenter study to assess the tolerability and efficacy of the addition of midostaurin to 10-day decitabine in unfit (i.e. HCT-CI ≥ 3) adult AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) patients. A study in the frame of the masterprotocol of parallel randomized phase II studies in UNFIT- AML/high-risk MDS patients.

Recruitment completed

HOVON 156

A phase 3, multicenter, open-label, randomized, study of Gilteritinib versus Midostaurin in combination with induction and consolidation therapy followed by one-year maintenance in patients with newly diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic syndromes with excess blasts-2 (MDS-EB2) with FLT3 mutations eligible for intensive chemotherapy.

HOVON 173

Ivosidenib and azacitidine with or without venetoclax in adult patients with newly diagnosed IDH1-mMutated AML or MDS/AML considered ineligible for intensive chemotherapy