Decitabine + Filgrastim for Acute Myeloid Leukemia

(MORE Trial)

Recruiting at 1 trial location

Overseen By Franziska Wachter, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Franziska Wachter

Disqualifiers: Uncontrolled illness, FLT3/ITD mutations, 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

Compensation: Varies

Number of Visits: 12

Duration: 6 months

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, decitabine (a chemotherapy drug) and filgrastim (a medication that stimulates white blood cell production), to determine if they can prevent relapse in children and young adults after a stem cell transplant for certain blood disorders like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The study evaluates the effectiveness and safety of this treatment post-transplant. Suitable candidates for this trial include those who have undergone a stem cell transplant for these blood disorders and are now in remission (showing no signs of disease). As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, your current medications should not have unacceptable interactions with the trial drugs. It's best to discuss your specific medications with the trial team.

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

Research shows that the combination of decitabine and filgrastim is under study for its potential to aid patients with high-risk acute myeloid leukemia (AML). Studies suggest this treatment might reduce the likelihood of cancer returning after a stem cell transplant.

Regarding safety, previous patients have demonstrated that this drug combination is generally well-tolerated. Filgrastim increases white blood cells, reducing infection risk during cancer treatment. Decitabine, a type of chemotherapy, targets cancer cells. While side effects like low blood cell counts are possible, these drugs are commonly used in other cancer treatments and are considered relatively safe for this purpose.

Since the current trial is in Phase 2, earlier studies have shown sufficient safety to proceed. However, discussing with a doctor is crucial to understand how this treatment might affect an individual personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Decitabine and Filgrastim for treating Acute Myeloid Leukemia (AML) because this combination could offer a new approach to managing the disease post-transplant. Unlike traditional chemotherapy, which directly targets and kills cancer cells, Decitabine works by altering the DNA of cancer cells, making them behave more like normal cells. Filgrastim, on the other hand, helps stimulate the growth of white blood cells, potentially reducing the risk of infections post-treatment. This combination aims to provide a more targeted and supportive therapy, which may improve patient outcomes and reduce treatment-related toxicities compared to standard chemotherapy options.

What evidence suggests that this trial's treatments could be effective in preventing relapse after HCT for acute myeloid leukemia?

This trial will evaluate the combination of decitabine and filgrastim for treating acute myeloid leukemia (AML). Research has shown that using decitabine and filgrastim together can help treat people with AML. One study, mostly involving adults with AML, found that this combination reduced the chance of cancer recurrence. This method seems especially helpful for patients at high risk. In this trial, participants in Cohort A, who are at standard risk, and Cohort B, who have an inherited bone marrow failure with increased risk, will receive decitabine and filgrastim after a stem cell transplant. Early results suggest this treatment could help prevent disease recurrence after the transplant in children and young adults with AML and similar conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Franziska Wachter, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 39 with myeloid malignancies like AML or MDS, who are undergoing stem cell transplants. They must be in remission, HIV-positive patients on effective therapy can join, as well as those with treated hepatitis B or C. Pregnant women cannot participate, and participants need a good performance status without severe heart disease.

Inclusion Criteria

I agree to use birth control during the study.

Registration can occur from day -30 to day -10 prior to stem cell infusion

I am in remission and show no minimal residual disease after a stem cell transplant.

Exclusion Criteria

Participants enrolled in another study prohibiting initiation of maintenance therapy

Inability to present for clinic visits for at least 7 months after study treatment initiation

I have severe side effects from previous cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive decitabine and filgrastim in cycles post allogenic HCT

6 months

6 cycles of 28 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up visit every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Filgrastim

Trial Overview The study tests the feasibility of using decitabine (a DNA methylation inhibitor) combined with filgrastim (a bone marrow stimulant) after stem cell transplant to prevent cancer relapse in young patients with certain blood disorders.

How Is the Trial Designed?

Group I: Cohort B: inherited bone marrow failure (iBMF) with Increased Risk for treatment related toxicities Experimental Treatment 2 Interventions

Participants with MDS, AML, AML/MDS, tAML/MDS with iBMF with increased risk for treatment related toxicities will be enrolled and will undergo study procedures as outlined: * Cycles 1: Study treatment must occur 40 - 120 days post allogenic HCT. * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Cycles 2 - 6: * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Follow up visit every 6 months for 24 months post allogenic HCT.

Group II: Cohort A: Standard Risk Experimental Treatment 2 Interventions

Participants with MDS, AML, AML/MDS, treatment related myeloid neoplasm (tAML/MDS) with either idiopathic disease or inherited bone marrow failure syndrome (iBMF) with standard risk for treatment related toxicities will be enrolled and will undergo study procedures as outlined: * Cycles 1: Study treatment start must occur 40 - 120 days post allogenic HCT. * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Cycles 2 - 6: * Day 2 - 6 of 28-day cycle: Predetermined dose of Decitabine. * Day 1 - 6 of 28-day cycle: Predetermined dose of Filgrastim. * Follow up visit every 6 months for 24 months post allogenic HCT.

Who Is Running the Clinical Trial?

Franziska Wachter

Lead Sponsor

Trials

1

Recruited

40+

Harvard Clinical and Translational Science Center (Harvard Catalyst)

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

Decitabine, administered at a dose of 20 mg/m² for 5 consecutive days, has been approved for older patients (≥65 years) with acute myeloid leukaemia (AML) who cannot undergo standard treatment, showing clinically meaningful improvements in overall survival after extended follow-up.

In a pivotal phase III trial, decitabine demonstrated significantly higher complete remission rates compared to standard treatment options like cytarabine, with a safety profile similar to cytarabine, including common side effects like fever and low blood cell counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine: a review of its use in older patients with acute myeloid leukaemia. Curran, MP.[2021]

Decitabine is a DNA methyltransferase inhibitor with a long history of antileukemic efficacy, particularly effective in treating acute myeloid leukemia in older patients or those unable to undergo intensive therapy.

The current dosing regimen of decitabine (20 mg/m² for 5 days) has been refined to minimize nonhematologic toxicity, making it a promising option for patients who may not tolerate more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine for acute myeloid leukemia. Marks, PW.[2018]

In a study of 125 patients with acute myeloid leukemia (AML), the combination of decitabine with the HAG regimen resulted in a higher total response rate (84.38%) compared to HAG treatment alone (65.63%), indicating improved treatment efficacy.

The combined treatment also enhanced immune function, as evidenced by increased levels of CD4+ and CD4+/CD8+ cells, while reducing levels of bFGF and VEGF, without increasing the incidence of adverse reactions compared to HAG alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic effect of decitabine combined with HAG in acute myeloid leukemia: a retrospective case-control analysis. Yi, K., Xu, SH., Cheng, H., et al.[2023]

In a study of 45 elderly patients (average age 68.5) with high-risk MDS and MDS-transformed AML, the decitabine combined with CEG regimen (DCEG) showed a significantly higher overall response rate (86.4%) compared to the decitabine combined with CAG regimen (47.8%).

Patients treated with the DCEG regimen also experienced longer overall survival (10 months) and progression-free survival (9 months) compared to those on the CAG regimen, indicating that DCEG may be a more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen]. Wu, M., Ma, IX., Xie, YH., et al.[2022]

In a study of 96 elderly patients with acute myeloid leukemia, the combination of decitabine with the CAG regimen showed a significantly higher total effective rate and improved 9-month and 1-year survival rates compared to the CAG regimen alone.

The combination therapy effectively inhibited cellular immune function without increasing the incidence of adverse reactions, indicating it is a safe and promising treatment option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine combined with CAG regimen in the treatment of elderly patients with acute myeloid leukemia. Zhao, H., Wang, C., Yu, F., et al.[2022]

In a study of 76 middle-aged and elderly patients with MDS-transformed AML, the combination of decitabine and pre-excitation chemotherapy (D+CTG) showed a significantly higher overall response rate (72%) compared to pre-excitation chemotherapy alone (CTG group at 50%).

Patients treated with D+CTG had a longer median survival time of 19.9 months compared to 11.0 months for those receiving CTG, with no increase in adverse reactions, indicating that this combination therapy is both effective and safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of Decitabine Combined with Pre-Excitation Chemotherapy in the Treatment of Middle-Aged and Elderly MDS Transformed Acute Myeloid Leukemia]. Li, ZK., Lai, YC., Li, K., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7768335/

Effect of rhG-CSF Combined With Decitabine Prophylaxis ... The prognosis of patients with high-risk (HR) acute myeloid leukemia (AML) continues to worsen after treatment. One potentially curative regimen for HR-AML is ...

2. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05796570

NCT05796570 | A Pilot Study to Evaluate the Feasibility of ... Decitabine in combination with filgrastim ... effective in a large study that included mainly adult patients with acute myeloid leukemia.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03484

Decitabine in Combination with Filgrastim Post- ... Giving decitabine in combination with filgrastim post-HCT may help decrease the risk of relapse in pediatric and young adult patients with AML, MDS, and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7410295/

Outcomes of decitabine treatment for newly diagnosed acute ... We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors.

5. emedicine.medscape.com emedicine.medscape.com/article/2004793-overview

Acute Myeloid Leukemia (AML) Treatment Protocols Treatment protocols for acute myeloid leukemia are provided below, including a general treatment approach and treatment recommendations for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07012044

NCT07012044 | A Study to Find the Highest Dose of ... Giving ATSX727 and filgrastim may be safe and tolerable in treating children with high risk, recurrent or refractory acute myeloid leukemia who ...

7. neupogenhcp.com neupogenhcp.com/acute-myeloid-leukemia

Patients with Acute Myeloid Leukemia (AML) Receiving ... NEUPOGEN is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment.