Genomic Assessment for Mutation Clearance in Acute Myeloid Leukemia

Not currently recruiting at 3 trial locations

Overseen By Meagan Jacoby, M.D., Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Disqualifiers: APL, Therapy-related AML, Secondary AML, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether individuals with acute myeloid leukemia (AML) who clear certain genetic mutations with chemotherapy have better outcomes compared to historical data. Participants will receive cytarabine, a chemotherapy drug, with the treatment plan tailored to specific mutations. Suitable candidates for this trial include those with a type of AML not related to previous cancer treatments, who are in remission after initial treatment but have not fully recovered their blood counts. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant advancements in AML treatment.

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

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

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

Research shows that cytarabine commonly treats certain types of leukemia, such as acute myeloid leukemia (AML). Studies have found it is usually well-tolerated, but it can cause side effects. Common side effects include nausea, vomiting, and low blood cell counts, which can lead to infections or bleeding. Some patients might also experience liver issues or a skin rash.

High-dose cytarabine, known as HiDAC, is often used in treatment plans and has proven effective. Patients should know that side effects can intensify at higher doses, potentially causing eye irritation or nervous system issues, such as confusion or balance problems.

Cytarabine is part of standard leukemia treatments and has received FDA approval for this use, indicating a good understanding of its safety. However, anyone considering joining a trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they focus on personalized strategies for tackling acute myeloid leukemia (AML). Unlike traditional approaches, which might use a one-size-fits-all method, this trial uses genomic assessment to determine the best course of action. For patients with persistent mutations, the investigator can choose between high-dose cytarabine (HiDAC) or an allogeneic stem cell transplant (AlloSCT), offering a tailored approach based on genetic markers. Meanwhile, patients showing mutation clearance receive HiDAC as a consolidation therapy, with the potential addition of an FLT3 inhibitor for certain mutations. This personalized strategy aims to improve outcomes by targeting specific cancer characteristics, making it a promising frontier in AML treatment.

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

Studies have shown that high-dose cytarabine (HiDAC), which participants in this trial may receive, effectively treats acute myeloid leukemia (AML). Some treatment plans using cytarabine have achieved cure rates of 75–80% in certain cases. In this trial, patients with ongoing leukemia-related genetic changes may receive a stem cell transplant from a donor (alloSCT) as another treatment option. Research indicates that this type of transplant can improve survival rates, with some studies showing about 40% of patients living at least five years after the procedure. Both treatments in this trial aim to improve outcomes for people with AML, but their effectiveness can vary based on individual patient factors. ^{6 7 8 9 10}

Who Is on the Research Team?

Meagan Jacoby, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with previously untreated, non-M3 Acute Myeloid Leukemia (AML) of intermediate risk or normal cytogenetics with specific mutations. Participants must be in remission post-induction therapy and agree to use contraception. Excluded are those with AML due to prior chemo/radiation, other hematological malignancies, significant medical issues affecting compliance, known HIV/HBV/HCV infections, or pregnancy.

Inclusion Criteria

I am considered a good candidate for intensive chemotherapy.

My AML is untreated, not M3 type, and is intermediate-risk or has specific genetic features.

My blood cancer is in remission but my blood counts haven't fully recovered.

Exclusion Criteria

History of allergic reaction to compounds of similar chemical or biologic composition to cytarabine

Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 3 days of signing consent

Has medical or psychosocial conditions that would prevent study compliance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard consolidation chemotherapy or alloSCT based on mutation clearance status

12-16 weeks

Multiple visits for chemotherapy cycles

Follow-up

Participants are monitored for relapse-free and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic stem cell transplant
• Bone marrow aspiration
• Cytarabine
• Punch skin biopsy

Trial Overview The study tests if clearing leukemia-associated mutations using standard chemotherapy improves survival compared to historical data. It also assesses outcomes for patients whose mutations persist and may receive either chemotherapy or a stem cell transplant based on the physician's discretion.

How Is the Trial Designed?

Group I: Cohort B: Investigator's choice (HiDAC, AlloSCT) Experimental Treatment 5 Interventions

* At the time of diagnostic bone marrow biopsy, samples will be clinically sequenced via ClinSeq * Patients who have persistent leukemia-associated mutations, defined as a LAM VAF ≥2.5% will be assigned to the investigator's choice arm. * Patients assigned to this arm may received either HiDAC or AlloSCT. * HiDAC = Standard regimen of cytarabine 1.5 g/m\^2 or 3 g/m\^2 over 2-3 hours twice a day on Days 1, 3, \& 5 of each 28 day cycle for 3-4 cycles. Can be replaced by Onureg with permission from PI. * The source of stem cell product, donor selection, conditioning regimen, graft-versus-host-prophylaxis, and supportive care will be at the discretion of the treatment physician * For patients with the FLT3-ITD or a FLT3-TKD mutation, therapy with the FDA-approved FLT3 inhibitor midostaurin is permitted at the discretion of the treating physician.

Group II: Cohort A: HiDAC Experimental Treatment 4 Interventions

* At the time of diagnostic bone marrow biopsy, samples will be clinically sequenced via ClinSeq * Patients who have clearance of their leukemia-associated mutations, defined as a LAM VAF \<2.5% will be assigned to the high-dose cytarabine consolidation (HiDAC) arm. * HiDAC = Standard regimen of cytarabine 1.5 g/m\^2 or 3 g/m\^2 over 2-3 hours twice a day on Days 1, 3, \& 5 of each 28 day cycle for 3-4 cycles. Can be replaced by Onureg with permission from PI. * For patients with the FLT3-ITD or a FLT3-TKD mutation, therapy with the FDA-approved FLT3 inhibitor midostaurin is permitted at the discretion of the treating physician.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

American Society of Hematology

Collaborator

Trials

14

Recruited

20,800+

Published Research Related to This Trial

The MiSeq next-generation sequencing platform effectively screened 54 cancer-related genes in 63 samples from patients with acute myeloid leukemia, showing complete concordance with results from other established testing methods.

MiSeq demonstrated high accuracy in detecting mutations at low frequencies (as low as 1.5%) and offers advantages such as a quick 4-day turnaround time and the ability to assess both routine and emerging genetic markers, making it a promising tool for clinical applications in monitoring and treating acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation sequencing-based multigene mutational screening for acute myeloid leukemia using MiSeq: applicability for diagnostics and disease monitoring. Luthra, R., Patel, KP., Reddy, NG., et al.[2021]

Next generation sequencing (NGS) has significantly advanced the understanding of acute myeloid leukemia (AML) by identifying genetic mutations and precursor lesions, which are now influencing treatment decisions and patient stratification.

The integration of genetic profiling into clinical practice is expected to enhance diagnosis, risk assessment, and the development of personalized treatment plans, including the use of recently approved drugs targeting specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation Sequencing in AML-On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation? Leisch, M., Jansko, B., Zaborsky, N., et al.[2020]

A new diagnostic approach combining karyotyping and mutational screening using next-generation sequencing allows for rapid and accurate risk stratification in acute myeloid leukemia, significantly speeding up treatment decisions.

In a validation study with 22 patient samples, this method correctly identified 97% of copy number variations and accurately classified all tested karyotypes, demonstrating its potential to enhance subtype-specific therapies for leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive genetic diagnosis of acute myeloid leukemia by next-generation sequencing. Mack, EKM., Marquardt, A., Langer, D., et al.[2020]

Acute myeloid leukemia (AML) is becoming more common, especially in older populations, and traditional chemotherapy treatments are often ineffective for most patients, highlighting the need for more personalized approaches.

Recent advancements in molecular technologies have identified new genetic mutations and changes in AML, which can help tailor more effective, individualized treatment strategies that combine targeted therapies with conventional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Myeloid Leukemia: Biologic, Prognostic, and Therapeutic Insights. Khaled, S., Al Malki, M., Marcucci, G.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5735966/

Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia The 5-year overall survival (OS) and event-free survival for the entire cohort was 40.1 ± 3.5% and 38.7 ± 3.4%, respectively. The 5-year OS for patients in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2531137925001555

OUTCOMES OF ALLOGENEIC STEM CELL ... Despite intensive chemotherapy, 10%–40% of AML patients fail to achieve remission. Even among young adult patients who reach remission, relapse occurs in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12533790/

Outcomes of Allogeneic Hematopoietic Stem Cell ... Haploidentical HSCT improved one-year survival (77.9% vs. 62.0% with chemotherapy) in elderly AML, with lower relapse (16.5% vs. 56.6%). Matched ...

4. nature.com nature.com/articles/s41408-024-01060-4

Continuously improving outcome over time after second ... Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT ( ...

5. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/outcomes-after-stem-cell-transplant-in-elderly-patients-with-acute-myeloid-leukemia-have-improved-since-2000/

Outcomes After Stem Cell Transplant in Elderly Patients ... Leukemia-free survival climbed from 32% to 38% to 44% across the three time periods, while overall survival climbed from 37% to 42% to 49%. The ...

6. drugs.com drugs.com/mtm/cytarabine.html

Cytarabine Uses, Side Effects & Warnings Cytarabine is used together with other cancer drugs to treat certain types of leukemia (blood cancers). Cytarabine is also used to treat or prevent leukemia ...

7. healio.com healio.com/clinical-guidance/drugs/cytarabine

Cytarabine: Uses, Side Effects & Dosage Find clinical guidance on Cytarabine, including indications, dosing, safety, side effects and evidence-based insights for healthcare ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557680/

Cytarabine - StatPearls - NCBI Bookshelf Cytarabine is a medication used in the management and treatment of leukemias and lymphomas. It belongs to the antimetabolic group of medications.

9. asco.org asco.org/abstracts-presentations/ABSTRACT74020

Etoposide and cytarabine as an effective and safe ... Timed sequential therapy with high-dose cytarabine and mitoxantrone as an effective and safe induction regimen for acute myeloid leukemia. First Author: Melissa ...

10. rxlist.com rxlist.com/cytarabine-drug.htm

Cytarabine (Cytarabine): Side Effects, Uses, Dosage, ... Cytarabine for Injection (Brand Names: Cytosar-U, Tarabine PFS) is a cancer medication used to treat certain types of leukemia (blood cancers).