This phase I trial studies the side effects and preliminary efficacy of ziftomenib in combination with venetoclax and azacitidine in treating pediatric patients with acute leukemias that have come back after a period of improvement (relapsed) or that do not respond to treatment (refractory). Ziftomenib prevents the interaction between two proteins, menin and MLL, that are needed for cancer cells to grow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. In this trial, the safety, tolerability, and preliminary efficacy of ziftomenib in combination with venetoclax and azacitidine in pediatric acute leukemias will be investigated.
Additional locations may be listed on ClinicalTrials.gov for NCT06397027.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: David McCall
Phone: 713-792-6604
PRIMARY OBJECTIVE:
I. To determine the safety, tolerability, and recommended phase II dose (RP2D) of ziftomenib in combination with venetoclax and azacitidine for pediatric patients with acute leukemias with KMT2A-rearrangement(r), NPM1-mutation(m) or NUP98-r.
SECONDARY OBJECTIVE:
I. To determine the preliminary assessment of efficacy by overall response (OR), including complete remission (CR), CR with partial hematological recovery (CRh), CR with incomplete blood count recovery (CRi), morphological leukemia-free state (MLFS) and partial remission (PR), overall survival (OS), event-free survival (EFS) and duration of response (DOR) of pediatric patients treated with this combination.
EXPLORATORY OBJECTIVE:
I. To evaluate molecular and cellular markers that may be predictive of antitumor activity and/or resistance.
OUTLINE: This is a phase I dose-escalation study of ziftomenib in combination with azacitidine and venetoclax followed by a dose-expansion study.
Patients receive ziftomenib orally (PO) on days 8-28 and venetoclax PO on days 1-14 and azacytidine intravenously (IV) on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease (PD) discontinue study treatment. Patients also undergo bone marrow biopsy and/or aspiration, as well as blood sample collection throughout the trial.
After completion of study treatment, patients are followed up monthly for 3 years.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorDavid McCall