In short
Clinical trials are studying Ziftomenib in people with acute leukemia, including adults and children with relapsed, refractory, or newly diagnosed disease. These studies look at safety, the best dose, how the drug behaves in the body, and whether it helps with treatment outcomes.
Key points
- Ziftomenib is being studied in clinical trials for acute leukemia, especially acute myeloid leukemia. The trial program includes adults with relapsed or refractory disease, adults with newly diagnosed AML with certain genetic changes, and children with relapsed or refractory acute leukemia. The studies range from Phase 1 to Phase 3, so they cover early dose-finding work and later testing of treatment benefit. Main goals include finding the right dose, checking safety, and measuring how well the treatment works. The trials also look at outcomes such as complete remission, overall survival, event-free survival, and pharmacokinetics.
Trial overview
The clinical trial program for Ziftomenib is focused on acute leukemia, especially acute myeloid leukemia (AML), and also includes some related blood cancers. The studies are testing Ziftomenib in different settings: as a first-in-human treatment in adults with relapsed or refractory disease, in children with relapsed or refractory acute leukemia, and in adults with newly diagnosed AML that has specific genetic changes.
These trials are interventional studies, which means the researchers give a treatment and then measure the results. The phases range from Phase 1 to Phase 3, so the program includes early testing for safety and dose, as well as larger studies that look at treatment benefit.
Adult relapsed or refractory AML studies
NCT04067336 is a Phase 1/2 study in adults with relapsed or refractory AML. “Relapsed” means the cancer came back after treatment, and “refractory” means it did not respond well to treatment. This study is authorised and plans to enroll 205 people.
The early part of this trial looks for the maximum tolerated dose, which is the highest dose that can be given without too many serious problems, and the recommended phase 2 dose, which is the dose chosen for later studies. Later parts of the study look at safety, tolerability, and signs that the treatment may be helping.
This trial also includes sub-studies. One sub-study measures pharmacokinetics, which means how Ziftomenib and its breakdown products move through the body. Other sub-studies look at activity in adults with KMT2A-rearranged acute lymphoblastic leukemia and in AML with mutations linked to MEIS1 overexpression.
Children’s study with chemotherapy
NCT06376162 is a Phase 1 study in children with relapsed or refractory acute leukemia. The study includes acute myeloid leukemia, mixed phenotype acute leukemia, and acute lymphocytic leukemia. It is authorised and plans to enroll 20 participants.
This study tests Ziftomenib together with chemotherapy, including fludarabine and cytarabine, and also intrathecal Solu-Cortef in one part of the treatment plan. Intrathecal means the medicine is given into the fluid around the brain and spinal cord. The main goal is to find the recommended phase 2 dose based on dose-limiting toxicities and pharmacokinetic results.
Dose-limiting toxicities are side effects that are serious enough to limit how much treatment can be given. The study also includes children with specific genetic types of acute leukemia, including KMT2A-rearranged, NUP98-rearranged, and NPM1-mutated disease.
Phase 3 study in newly diagnosed AML
NCT07007312 is a Phase 3 study for adults with newly diagnosed AML that has either an NPM1 mutation or a KMT2A rearrangement. It is authorised and has the largest planned enrollment in this set of trials, with 1,320 participants.
This study compares Ziftomenib with standard treatment approaches in two settings. In the nonintensive therapy study, it is tested with venetoclax and azacitidine, and the main outcome is overall survival. In the intensive therapy study, it is tested with standard 7+3 chemotherapy, and the main outcome is event-free survival.
Overall survival means how long people live after treatment starts, and event-free survival means how long people stay free from treatment failure, relapse, or death. This Phase 3 study is important because it is designed to test whether adding Ziftomenib can improve major patient outcomes in newly diagnosed AML with these genetic changes.
Key outcomes being measured
The trial program measures several important outcomes across different phases. Early studies focus on safety, tolerability, dose selection, and pharmacokinetics.
In the adult Phase 1/2 study, researchers also track complete remission and complete remission with partial hematologic recovery, which are signs that the blood cancer has responded to treatment. In the Phase 3 study, the main outcomes are overall survival in the nonintensive arm and event-free survival in the intensive arm.
In the children’s Phase 1 study, the main goal is to choose the best dose for later testing using safety and drug exposure data. Drug exposure means how much of the drug gets into the body and how long it stays there.
Who may join these trials
The adult studies are for people with AML, especially those with relapsed or refractory disease or newly diagnosed disease with NPM1 mutation or KMT2A rearrangement. The child study is for children with relapsed or refractory acute leukemia, including AML, mixed phenotype acute leukemia, and acute lymphocytic leukemia.
Some parts of the adult Phase 1/2 study also include people with KMT2A-rearranged acute lymphoblastic leukemia and AML with MEIS1-related mutations. Because each trial has its own rules, the exact group that can join depends on the study and the disease features being tested.