Ziftomenib for Acute Myeloid Leukemia

Overseen By Zachariah DeFilipp, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Active hepatitis, Heart failure, Arrhythmias, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effects of a new drug, ziftomenib, to determine if it improves outcomes for people with acute myeloid leukemia (AML) who have undergone allo-HCT, a specific type of blood cancer treatment. The trial aims to find the right dose and assess its effectiveness when added to standard care. Participants should have AML in remission and test positive for specific genetic mutations related to their cancer. As a Phase 1 trial, this 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 need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ziftomenib is likely to be safe for humans?

Research shows that ziftomenib holds promise for treating certain types of acute myeloid leukemia (AML). In studies with patients whose AML returned or did not respond to other treatments, ziftomenib provided significant benefits. Importantly, patients tolerated it well, with manageable side effects, even after many previous treatments. This suggests ziftomenib may be a safe option for these patients, especially since they have few other treatment choices.

While these findings are encouraging, the current studies remain in the early stages. Although initial results are positive, researchers are still learning about the full safety profile of ziftomenib. However, early evidence suggests it could be a well-tolerated treatment option for AML patients after a stem cell transplant. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia, which often include chemotherapy and targeted therapies like FLT3 inhibitors, ziftomenib offers a novel approach by targeting the menin-MLL interaction. This is a unique mechanism of action that can disrupt cancer cell growth differently than existing options. Researchers are excited about ziftomenib because it is designed to work even in cases that have relapsed or are resistant to current treatments, potentially offering new hope for patients who have limited options. Additionally, its oral administration makes it more convenient compared to some existing therapies that require hospitalization or infusion.

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

Research has shown that ziftomenib holds promise for treating acute myeloid leukemia (AML), particularly in patients with genetic changes like NPM1 mutations. In studies, ziftomenib proved effective and had manageable side effects for patients who did not respond to other treatments. Some patients experienced improvements in less than two months, while others took longer. The drug blocks harmful interactions inside cancer cells, potentially improving survival rates when combined with standard treatments. In this trial, all participants will receive ziftomenib after a bone marrow transplant, indicating it could be a viable option for AML patients in this context. ^{2 3 4 6 7}

Who Is on the Research Team?

Zachariah DeFilipp, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with Acute Myeloid Leukemia (AML) who have a specific NPM1 mutation and have undergone Allogeneic Hematopoietic Cell Transplantation (allo-HCT). Participants should meet certain health standards, which will be specified by the researchers.

Inclusion Criteria

My cancer is in complete remission.

Participants must have a HCT donor meeting specific criteria

My organs are functioning normally.

Exclusion Criteria

Persons who are pregnant or lactating

I have had cancer before, but it meets the trial's specific criteria.

QTc interval ≥ 480 ms or other risk factors for QT prolongation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

30 days

Treatment

Participants receive ziftomenib orally once per day for up to 12 months following allo-HCT

12 months

Monthly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Quarterly visits for data collection

What Are the Treatments Tested in This Trial?

Interventions

• Ziftomenib

Trial Overview The study is testing ziftomenib's safety and effectiveness when used after allo-HCT in AML patients. Ziftomenib aims to block harmful interactions within cancer cells. The goal is to see if it can improve patient outcomes post-transplant.

How Is the Trial Designed?

Group I: Ziftomenib Experimental Treatment 1 Intervention

Participants will begin treatment 30 to 90 days after allo-HCT and only after disease remission is confirmed, and treatment will continue for up to 12 months. All participants will receive ziftomenib. Participants will undergo allo-HCT as a part of their standard care. Participants will undergo the following procedures: * Screening * Allo-HCT (standard care), including pre and post-treatment as a part of standard care * 30 - 90 days after allo-HCT, participants will take the study drug orally once per day for up to 12 28-day cycles * End of treatment visit * Follow-up data will be collected every 3 months for 24 months from the start of treatment

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Gemtuzumab Ozogamicin (GO) has been approved for treating newly diagnosed CD33+ acute myeloid leukemia (AML) in combination with daunorubicin and cytarabine, offering new therapeutic options for patients.

Key biomarkers such as elevated CD33 expression and favorable cytogenetic profiles have been identified as predictors of a good response to GO, helping clinicians tailor treatments more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin. Gottardi, M., Simonetti, G., Sperotto, A., et al.[2021]

In a phase I trial, the investigational drug KO-539, a menin-MLL inhibitor, demonstrated the ability to induce complete remissions in two patients with acute myeloid leukemia (AML) who had relapsed or refractory disease.

The trial also indicated signs of activity in several other patients, suggesting potential efficacy of KO-539 in treating AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AML Prognoses Better with Menin-MLL Inhibitor? [2021]

Acute myeloid leukemia (AML) primarily affects older adults, with 35% of new cases diagnosed in patients aged 75 and older, and they generally have poorer responses to standard chemotherapy due to unique biological factors and higher comorbidity rates.

Recent advancements in treatment, including the introduction of gemtuzumab ozogamicin and ongoing clinical trials for new therapies, are changing the treatment landscape for elderly AML patients, aiming to improve their outcomes compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging strategies for the management of acute myeloid leukemia in the elderly. Laubach, J., Rao, AV.[2008]

Acute myeloid leukemia (AML) has the lowest survival rate among leukemias, particularly affecting elderly patients, highlighting the urgent need for new treatment strategies.

Emerging therapies such as Gemtuzumab ozogamicin for CD33-positive AML and selective FLT3 inhibitors show promise in improving survival rates, indicating potential advancements in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidemiology and clinical burden of acute myeloid leukemia. Redaelli, A., Lee, JM., Stephens, JM., et al.[2007]

Acute myeloid leukemia (AML) remains a challenging disease with only about 60% 5-year survival for patients classified as favorable risk, highlighting the need for better treatment options, especially for the elderly.

Recent advancements include the use of clofarabine for relapsed disease and hypomethylating agents, but clinical trials for FLT3 inhibitors have not shown promising results, indicating a need for ongoing research into new therapies targeting leukemia stem cells and minimal residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia: focus on novel therapeutic strategies. Lin, TL., Levy, MY.[2022]

Citations

1. 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 shows promising results in treating relapsed/refractory acute myeloid leukemia with NPM1 mutations, offering hope for improved ...

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

Ziftomenib in Relapsed or Refractory NPM1-Mutated AML In this trial, the median time to response was 1.9 months, with some patients requiring up to 3.7 months of continuous therapy to achieve ...

3. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00386-3/abstract

Ziftomenib in relapsed or refractory acute myeloid ... Ziftomenib showed promising clinical activity with manageable toxicity in heavily pretreated patients with relapsed or refractory acute myeloid ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10543165/

Menin inhibitor ziftomenib (KO-539) synergizes with drugs ... Zifomenib acts highly selective in MLL-r and NPM1mut acute myeloid leukemia and synergizes with a variety of targeted drugs in vitro. (A) Dose-response curve ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04067336

NCT04067336 | First in Human Study of Ziftomenib ... This first-in-human (FIH), open-label study will assess ziftomenib, a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory (R/R) acute myeloid ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39362248/

Ziftomenib in relapsed or refractory acute myeloid ... Background: Ziftomenib (KO-539) is an oral selective menin inhibitor with known preclinical activity in menin-dependent acute myeloid leukaemia models. The ...

7. ir.kuraoncology.com ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-provides-update-phase-1b-study-ko-539-acute

Kura Oncology Provides Update on Phase 1b Study of KO- ... The US Food and Drug Administration (FDA) has placed the KOMET-001 Phase 1b study of KO-539 in patients with relapsed or refractory acute myeloid leukemia (AML ...