Ziftomenib + Venetoclax + Gemtuzumab for Acute Myeloid Leukemia

Overseen By Branko Cuglievan, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy, Antileukemic agents

Disqualifiers: Chronic liver disease, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications to determine the best dose for treating children and young adults with certain types of leukemia that have returned or resisted treatment. The medications under investigation are ziftomenib (an experimental treatment), gemtuzumab, and venetoclax, which aim to target and kill cancer cells more effectively. Suitable candidates have leukemia with specific genetic markers and have experienced a return or resistance of their disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but it does not allow other chemotherapeutic or anti-leukemic agents during the study, except for certain cases like intrathecal chemotherapy for CNS leukemia or hydroxyurea for rapidly proliferative disease. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ziftomenib, one of the treatments being tested, has produced promising results in patients with acute myeloid leukemia (AML) who haven't responded to other treatments. It has manageable side effects, meaning that while some side effects exist, they aren't severe for most participants in earlier studies.

Venetoclax, another treatment in this trial, already has FDA approval for AML and some other blood cancers. Previous studies have demonstrated its predictable safety profile, meaning doctors know what side effects to expect, and they're generally manageable.

Gemtuzumab ozogamicin, the third treatment, has been successfully used in both adults and children with AML. It's generally well-tolerated, meaning most people can handle the treatment without major problems.

This trial focuses on finding the right dose of ziftomenib when used with the other two treatments. As an early-phase study, it primarily examines safety and how well participants can tolerate the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for acute myeloid leukemia (AML) because it introduces a novel player, ziftomenib, which works differently from existing therapies. Most treatments for AML, like chemotherapy, target rapidly dividing cells indiscriminately, but ziftomenib specifically targets the menin-MLL1 protein-protein interaction, a crucial driver in some forms of leukemia. This targeted approach, combined with the synergistic effects of venetoclax, which inhibits BCL-2 proteins, and gemtuzumab, an antibody-drug conjugate, aims to enhance effectiveness while potentially reducing harmful side effects. By focusing on these specific mechanisms, this combination could offer a more precise and powerful treatment option for patients with AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that ziftomenib may benefit individuals with relapsed or hard-to-treat acute myeloid leukemia (AML), demonstrating positive effects with manageable side effects. Some patients experience improvements within a few months of starting treatment. When combined with other treatments, venetoclax has led to high remission rates in older AML patients. Additionally, gemtuzumab ozogamicin has effectively treated relapsed AML, with many patients responding well. This trial will explore the combination of these treatments, offering hope for better outcomes in challenging AML cases. ^{4 6 7 8 9}

Who Is on the Research Team?

Branko Cuglievan

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for pediatric patients with relapsed or refractory Acute Myeloid Leukemia (AML) or Mixed Phenotype Acute Leukemia (MPAL). Specific eligibility criteria details are not provided.

Inclusion Criteria

My kidneys work well enough (creatinine clearance ≥ 30 mL/min).

I am currently receiving treatment for brain disease prevention or control.

Baseline ejection fraction must be > 40%

Exclusion Criteria

I weigh less than 10kg.

I do not have severe active GVHD or chronic GVHD.

Mean corrected QT interval by Fredericia's formula >480 ms on triplicate 12-lead electrocardiograms performed within approximately 5 minutes of each other

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of ziftomenib in combination with gemtuzumab ozogamicin and venetoclax to determine the recommended Phase II dose

12-16 weeks

Dose Expansion

Participants receive the recommended Phase II dose of ziftomenib in combination with gemtuzumab ozogamicin and venetoclax to further assess safety and efficacy

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gemtuzumab
• Venetoclax
• Ziftomenib

Trial Overview The study aims to determine the appropriate dose of Ziftomenib when combined with Venetoclax and Gemtuzumab in children who have AML that has returned after treatment or hasn't responded to previous treatments.

How Is the Trial Designed?

Group I: Dose Escalation + Dose Expansion Experimental Treatment 3 Interventions

Participants found to be eligible to take part in this study, you will be assigned to a dose level of ziftomenib based on when you join this study. Up to 4 dose levels of ziftomenib will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the recommended dose of ziftomenib is found.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Kura Oncology, Inc.

Industry Sponsor

Trials

19

Recruited

1,700+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10813452/

Gemtuzumab Ozogamicin in Acute Myeloid Leukemia A study showed that when GO was administered as a single agent, it appeared to be an effective option for treating relapsed AML, with a 31.6% ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213048925000275

Real-World Efficacy and Safety of Gemtuzumab ... Gemtuzumab ozogamicin plus standard induction chemotherapy “3 + 7″ has been reported to improve outcomes of newly diagnosed intermediate cytogenetic risk AML, ...

3. ashpublications.org ashpublications.org/blood/article/142/20/1673/498629/Gemtuzumab-ozogamicin-in-AML-the-next-chapter

Gemtuzumab ozogamicin in AML: the next chapter | Blood The study results demonstrate for the first time in a large prospective way that higher cumulative GO doses delivered in 2 doses increased the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8841227/

Outcomes Of Adult Acute Myeloid Leukemia Treated With ... We report an ORR of 97% in newly diagnosed AML patients (n=37) with a median age of 54 (range, 19–75) years treated with GO in combination with ...

5. nature.com nature.com/articles/s41375-025-02700-9

Gemtuzumab ozogamicin in first-line treatment of CBF-AML In a contemporary cohort, our data show an absolute survival advantage of 10% at 2 years with GO-containing induction therapy and acceptable ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6312010/

Gemtuzumab ozogamicin for de novo acute myeloid ... Safety analyses. Safety data presented in this report were collected retrospectively and consist of events of special interest considered the most important ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6516

Safety outcomes in patients with acute myeloid leukemia ... Conclusions: The use of GO appears to be safe prior to HSCT in adults with AML. Rates for 100-day VOD and TRM were comparable to those ...

8. ashpublications.org ashpublications.org/blood/article/132/Supplement%201/3979/265258/Safety-of-Gemtuzumab-Ozogamicin-As-Monotherapy-or

Safety of Gemtuzumab Ozogamicin As Monotherapy or ... Previous studies have shown GO is generally well tolerated and can induce durable second remissions when administered as monotherapy or in ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4558626/

A Report From The Children's Oncology Group - PMC Safety and Efficacy of Gemtuzumab Ozogamicin in Combination With Chemotherapy for Pediatric Acute Myeloid Leukemia: A Report From The Children's Oncology Group.