Combining ziftomenib with venetoclax and gemtuzumab for children with acute myeloid leukemia

A Phase I Study Investigating the Combination of the Menin Inhibitor Ziftomenib With Venetoclax and Gemtuzumab in Pediatric Patients With Acute Myeloid Leukemia

This study is testing a new combination of medicines for children with tough cases of acute myeloid leukemia to see if it is safe and helps them feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 3 Years to 21 Years
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, gemtuzumab
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06448013 on ClinicalTrials.gov

What this trial studies

This study aims to determine the safety and optimal dosage of ziftomenib when used alongside venetoclax and gemtuzumab in pediatric patients suffering from relapsed or refractory acute myeloid leukemia (AML) or mixed phenotype acute leukemia (MPAL). The primary focus is on assessing the tolerability of this combination therapy, while secondary objectives include evaluating its efficacy through various response metrics such as overall survival and event-free survival. Additionally, the study will explore molecular and cellular markers that may indicate treatment response or resistance. Participants will be closely monitored for their response to the treatment and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 3 to 21 years with relapsed or refractory AML or MPAL and specific genetic mutations.

Not a fit: Patients with rapidly proliferative disease or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for pediatric patients with difficult-to-treat forms of leukemia.

How similar studies have performed: While this specific combination has not been extensively tested, similar approaches in targeting AML have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 3 year to 21 years
2. Karnofsky for children \>16yo and Lansky \<16yo.
3. Relapsed/refractory AML, or MPAL with a myeloid phenotype.

   1. Evidence of leukemia (AML, MPAL with a myeloid phenotype) in the bone marrow as detected by morphology or molecular diagnostics.
   2. Presence of KMT2Ar, NUP98r, NPM1c, UBTF-ITD or other HOX pathway mutation.
4. WBC must be below 25,000/ƒÊL at time of enrollment. Participants may receive cytoreduction prior to enrollment.
5. Baseline ejection fraction must be \> 40%.
6. Adequate hepatic function (direct bilirubin \< 1.5x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 3x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible).
7. Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease.
8. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for participants with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
9. 3 month washout prior from bone marrow transplantation.
10. Unless surgically or biologically sterile: Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months for males, and 6 months for females, after the last treatment.

Exclusion Criteria:

1. Participants who weigh less than 10kg.
2. Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
3. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
4. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
5. Participants with chronic liver disease.
6. Participants with a concurrent active malignancy under treatment.
7. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
8. Female participants who are pregnant or breast-feeding.
9. Participants has an active uncontrolled infection.
10. Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack.
11. Mean corrected QT interval by Fredericia's formula \>480 ms on triplicate 12-lead electrocardiograms performed within approximately 5 minutes of each other.
12. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the patient to participate.
13. Clinically active central nervous system (CNS) leukemia.
14. The use of topical steroids for cutaneous graft-versus-host disease (GVHD) or stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted.
15. Participants with Grade \> 2 active acute GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Branko Cuglievan, MD — M.D. Anderson Cancer Center
• Study coordinator: Branko Cuglievan, MD

Conditions Acute Myeloid Leukemia