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

Trial Summary

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.

How is the drug Ziftomenib unique in treating acute myeloid leukemia?

Ziftomenib is unique because it is a menin-MLL inhibitor, which is a novel approach in treating acute myeloid leukemia by targeting specific proteins involved in the disease's progression. This mechanism is different from traditional chemotherapy and other treatments, offering a new potential option for patients, especially those with relapsed or refractory disease. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to test the safety, effects, and recommended dose of an investigational drug, ziftomenib, in addition to the standard treatment on blood cancer with Allogeneic Hematopoietic Cell Transplantation (allo-HCT). This study plans to learn more about ziftomenib, which targets and inhibits negative interactions within cancer cells related to AML, when given after allo-HCT, to determine if it improves outcomes following allo-HCT. The name of the study drug involved in this study is: • Ziftomenib

Research Team

Zachariah DeFilipp, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Epidemiology and clinical burden of acute myeloid leukemia. [2007]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia: focus on novel therapeutic strategies. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Current and emerging strategies for the management of acute myeloid leukemia in the elderly. [2008]