Ziftomenib + Chemotherapy for Leukemia

Recruiting at 22 trial locations

Overseen By Dr. Sarah Tasian, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: LLS PedAL Initiative, LLC

Must not be taking: Proton pump inhibitors

Disqualifiers: Down syndrome, EMD, APL, JMML, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and dosage of ziftomenib, a potential new drug, combined with chemotherapy for a type of leukemia that has returned or is not responding to standard treatments. The study aims to determine the best dose for future trials by observing the drug's effects on the body. It seeks children and young adults with specific genetic types of leukemia that have relapsed or resisted treatment. Participants should have experienced a relapse or have a form of leukemia unresponsive to standard therapies. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that proton pump inhibitors are prohibited due to their effect on the absorption of ziftomenib. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that ziftomenib in combination with chemotherapy is likely to be safe for humans?

Research shows that ziftomenib is generally safe for patients with certain types of acute leukemia. Studies have found that side effects are manageable and similar to those observed previously. Some patients experienced differentiation syndrome, which occurs when cancer cells mature too quickly, but it was manageable. Importantly, no major issues with heart rhythm were reported. Previous trials also showed no significant drop in blood cells, indicating a low risk of infection or bleeding. Only a small number of patients discontinued treatment due to side effects. Overall, the evidence suggests that ziftomenib is safe for those considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment options for leukemia, which often revolve around conventional chemotherapy regimens, ziftomenib introduces a new mechanism of action by targeting specific proteins involved in cancer cell survival. Researchers are excited about ziftomenib because it offers a potentially more precise approach by working in combination with chemotherapy to enhance its effectiveness. This targeted action could result in better outcomes for patients, especially those who have not responded well to existing therapies.

What evidence suggests that ziftomenib might be an effective treatment for leukemia?

Research has shown that ziftomenib effectively treats certain types of acute myeloid leukemia (AML), particularly in patients with specific genetic changes like NPM1 and KMT2A. In earlier studies, 94% of newly diagnosed patients with these genetic changes experienced a significant reduction in cancer signs when treated with ziftomenib and chemotherapy. This indicates that most patients saw a noticeable improvement. In this trial, participants will receive ziftomenib combined with FLA chemotherapy, and those who respond well may continue with ziftomenib monotherapy. Additionally, ziftomenib has demonstrated strong and lasting effects in patients whose disease returned or did not respond to other treatments. Some patients no longer needed blood transfusions, improving their quality of life. These promising results suggest that ziftomenib could be a powerful option for difficult-to-treat leukemia. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for children with relapsed or refractory acute leukemia who have specific genetic alterations (KMT2A-r, NUP98-r, or NPM1-m). They must show a certain level of leukemic blasts in their bone marrow and not just isolated extramedullary disease. Participants should be aged 0-21 years, mostly under 18, and weigh at least 5 kg.

Inclusion Criteria

My tests show abnormal chromosomes in my cells.

My bone marrow sample shows more than 1% leukemia cells confirmed by tests.

I am 21 or younger and weigh at least 5 kg, with most participants being under 18.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Cycle 1

Participants receive escalating doses of ziftomenib in combination with FLA chemotherapy for 49 days

7 weeks

Daily visits for drug administration

Treatment Cycle 2

Participants continue with ziftomenib and FLA chemotherapy for 28 days if they respond to Cycle 1

4 weeks

Daily visits for drug administration

Extended Treatment

Participants may receive up to 10 additional cycles of ziftomenib monotherapy if there is a delay before HSCT

Up to 10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 13 months

What Are the Treatments Tested in This Trial?

Interventions

• Ziftomenib

Trial Overview The study aims to find the safest dose for Ziftomenib when combined with chemotherapy drugs Cytarabine and Fludarabine in children with certain types of acute leukemia. It will look at how well patients tolerate this combination and measure drug levels in the body.

How Is the Trial Designed?

Group I: Ziftomenib Experimental Treatment 3 Interventions

During Cycle 1 (49 days), participants will receive escalating doses of ziftomenib once daily (QD) on Days 8 to 49. Participants will also receive FLA chemotherapy consisting of fludarabine at a dose of 30 mg/m\^2 (1 mg/kg/dose in infants \<1 year of age or ≤10 kg) and cytarabine at a dose of 2000 mg/m\^2 (67 mg/kg/dose in infants \<1 year of age or ≤10 kg) QD on Day 1 to Day 5. Participants with \<5% blasts will continue ziftomenib monotherapy until Day 49. Participants with a response and \>5% blasts will continue to Cycle 2. During Cycle 2 (28 days), participants will receive escalating doses of ziftomenib QD on Day 1 to Day 28 in combination with FLA chemotherapy on Day 1 to Day 5. Participants who respond to treatment, but experience a delay prior to hematopoietic stem cell transplantation (HSCT), may receive up to 10 additional cycles (28 days) of ziftomenib monotherapy. Participants may also receive intrathecal therapy prophylaxis, if needed, during all cycles.

Who Is Running the Clinical Trial?

LLS PedAL Initiative, LLC

Lead Sponsor

Trials

4

Recruited

1,100+

PedAL BCU, LLC

Lead Sponsor

Kura Oncology

Collaborator

Trials

2

Recruited

110+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01694

Ziftomenib in Relapsed or Refractory NPM1-Mutated AML Twenty percent of patients achieved transfusion independence on therapy, which is associated with improved quality of life and symptom control. ...

2. targetedonc.com targetedonc.com/view/final-trial-data-shows-success-for-ziftomenib-in-npm1-aml

Final Trial Data Show Success for Ziftomenib in NPM1 AML Ziftomenib showed significant efficacy in relapsed/refractory NPM1-mutant AML, achieving deep, durable responses in the KOMET-001 trial. The ...

3. onclive.com onclive.com/view/ziftomenib-with-7-3-shows-early-promise-in-newly-diagnosed-npm1-mutated-kmt2a-rearranged-aml

Ziftomenib With 7+3 Shows Early Promise in Newly ... Ziftomenib combined with 7+3 chemotherapy shows a 94% objective response rate in newly diagnosed NPM1-mutated and KMT2A-rearranged AML patients.

4. physicianresources.roswellpark.org physicianresources.roswellpark.org/news/final-landmark-clinical-trial-data-demonstrates-deep-durable-responses-to-menin-inhibition-in-acute-leukemia-patients

Final Landmark Clinical Trial Data Demonstrates Deep ... Ziftomenib effective against recurrent/treatment-resistant disease · Could replace toxic, less-effective treatments for these patients · Study ...

5. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-presentations-ziftomenib

Press Release Kura Oncology and Kyowa Kirin Announce Presentations of Ziftomenib Ven/Aza Combination Data in Frontline and Relapsed/Refractory NPM1-m or KMT2A ...

6. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-publication-pivotal

Kura Oncology and Kyowa Kirin Announce Publication of ... Ziftomenib was well tolerated with a safety profile consistent with previously disclosed data. The most common grade ≥3 treatment-emergent ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6506

Ziftomenib in relapsed/refractory (R/R) NPM1-mutant acute ... Ziftomenib was well tolerated with limited myelosuppression and only 3% ziftomenib-related discontinuations. Taken together, these data support ...