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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine if it is feasible to administer decitabine and filgrastim after allogenic hematopoietic stem cell transplant (HCT) in children and young adults with myelodysplastic syndrome, acute myeloid leukemia and related myeloid disorders, and if the treatment is effective in preventing relapse after HCT. The names of the study drugs involved in this study are: * Decitabine (a nucleoside metabolic inhibitor) * Filgrastim (a recombinant granulocyte colony-stimulating factor (G-CSF)

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.

What data supports the effectiveness of the drug Decitabine combined with Filgrastim for treating acute myeloid leukemia?

Research shows that Decitabine, when used alone or in combination with other drugs, has been effective in treating acute myeloid leukemia, especially in older patients who are not candidates for standard intensive therapy. It has shown promise in improving survival rates and achieving complete remission in some cases. ^{1 2 3 4 5}

Is the combination of Decitabine and Filgrastim safe for treating acute myeloid leukemia?

Decitabine is generally well tolerated in older patients with acute myeloid leukemia, with common side effects including fever, low platelet counts, and anemia (low red blood cell count). Filgrastim, also known as G-CSF, is often used to help increase white blood cell counts and is generally considered safe, though it can cause bone pain and other mild side effects. ^{1 3 4 5 6}

How is the drug Decitabine + Filgrastim unique for treating acute myeloid leukemia?

Decitabine + Filgrastim is unique because it combines a DNA methyltransferase inhibitor (Decitabine) with a granulocyte colony-stimulating factor (Filgrastim) to enhance the body's ability to produce white blood cells, potentially improving treatment outcomes for older patients with acute myeloid leukemia who are not candidates for more intensive therapies. ^{1 2 3 4 5}

Research Team

Franziska Wachter, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

References

1. China 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]. [2019]

2. Italy pubmed.ncbi.nlm.nih.gov

The therapeutic effect of decitabine combined with HAG in acute myeloid leukemia: a retrospective case-control analysis. [2023]

3. Pakistan pubmed.ncbi.nlm.nih.gov

Decitabine combined with CAG regimen in the treatment of elderly patients with acute myeloid leukemia. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Decitabine for acute myeloid leukemia. [2018]

6. China 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]. [2022]