Decitabine + FLAG-Ida for Myeloid Malignancies

Overseen By Naveed Ali, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Anti-leukemia agents

Disqualifiers: Active CNS disease, Infections, Pregnancy, others

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

Compensation: Varies

Number of Visits: 8

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of treatments and radiation to identify the safest and most effective method for treating certain blood cancers prone to recurrence. It combines the drug decitabine with chemotherapy drugs, including cytarabine and idarubicin, and full-body radiation, followed by a donor stem cell transplant. This approach aims to eliminate cancer cells and create space for healthy new cells to grow. Suitable candidates have blood cancers such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) and have experienced relapse or resistance to previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in participants, offering them a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on any other approved or investigational anti-leukemia treatments while participating in this trial.

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

Research has shown that combining decitabine with FLAG-Ida is generally safe and well-tolerated. In earlier studies, no treatment-related deaths were reported. Common side effects affected blood cells, but these were expected and managed during the trial.

The FLAG-Ida treatment, which includes fludarabine, cytarabine, filgrastim, and idarubicin, proved safe for most people. Some patients experienced fever due to low white blood cell counts, with rates between 44% and 55%. Other issues, such as infections, were also noted but varied among patients.

Overall, the evidence suggests that while side effects like fever and infections occur, the treatment remains manageable and does not lead to severe complications for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Decitabine + FLAG-Ida for myeloid malignancies because it combines several chemotherapy agents with a unique approach. This treatment uses Decitabine in conjunction with the FLAG-Ida regimen—Fludarabine, Cytarabine, and Idarubicin—alongside a stem cell transplant, which is not typically part of standard regimens. Unlike other treatments, which mainly rely on single-agent or combination chemotherapies, this approach aims to enhance the effectiveness by incorporating a hematopoietic stem cell transplant (HCT) to potentially improve outcomes and reduce relapse rates. This novel combination could offer a more comprehensive attack on cancer cells, providing hope for better long-term remission for patients.

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

In this trial, participants will receive a combination of decitabine with the FLAG-Ida treatment, which has shown potential benefits for treating blood cancers like acute myeloid leukemia (AML). This combination helps the bone marrow produce healthy blood cells and eliminates abnormal ones. Decitabine, particularly when used with the FLAG-Ida treatment, may help patients with AML achieve remission, meaning the cancer is no longer detectable. The FLAG-Ida treatment has also been associated with longer periods where the cancer does not return or worsen. While exact results can vary, previous studies have shown promising outcomes with these treatments. ^{5 6 7 8 9}

Who Is on the Research Team?

Naveed Ali, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with high-risk myeloid malignancies, such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML) who are candidates for a stem cell transplant. Participants should not have other health conditions that could interfere with the trial.

Inclusion Criteria

My heart, liver, lungs, and kidneys are functioning well.

I had a stem cell transplant and my condition worsened more than 6 months after.

I am mostly independent and active.

Exclusion Criteria

HAPLOIDENTICAL DONOR: Patients with anti-donor-specific antibodies (anti-DSA) MFI < 5000 after desensitization treatment

I do not have any uncontrolled infections.

Pregnancy or lactation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemotherapy and Radiation

Participants receive decitabine, FLAG-Ida regimen, and total body irradiation before donor stem cell transplantation

3 weeks

Daily visits for treatment administration

Transplantation

Participants undergo hematopoietic cell transplantation (HCT) with donor peripheral blood stem cells

1 day

1 visit (in-patient)

Follow-up

Participants are monitored for safety, effectiveness, and disease response after treatment

Up to 2 years

Regular follow-up visits at 6 months, 1 year, and 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Decitabine
• Filgrastim
• Idarubicin

Trial Overview The trial is testing the effectiveness of decitabine combined with FLAG-Ida chemotherapy and total-body irradiation before a donor stem cell transplant. The goal is to see if this combination works better than standard treatments in preventing cancer relapse.

How Is the Trial Designed?

Group I: Treatment (decitabine, FLAG-Ida, HCT) Experimental Treatment 14 Interventions

DONORS: Participants undergo apheresis for collection of PBSCs on study. PATIENTS: Patients receive decitabine IV daily over 1 hour on days -12 to -10, -14 to -10, -16 to -10, or -19 to -10, filgrastim SC daily on days -9 to -4, idarubicin IV over 60 minutes daily on days -8 to -6, fludarabine IV over 30 minutes daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and undergo TBI BID on day -1 or 0 OR daily on days -1 and 0 in the absence of disease progression or unacceptable toxicity. Patients then undergo HCT (receive donor PBSCs via infusion) on day 0. Patients also undergo MUGA scan or ECHO during screening, chest X-rays and bone marrow aspiration and/or biopsy during screening and as clinically indicated, and collection of blood samples throughout the study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Published Research Related to This Trial

In a study of 44 patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), the combination of decitabine with the EIAG regimen resulted in a higher modified composite complete response (mCRc) rate of 72.7% compared to 40.9% in the CAG regimen group, indicating improved efficacy.

Both treatment regimens led to significant myelosuppression as a common adverse effect, but there was no increase in non-hematological toxicities, suggesting that decitabine combined with EIAG is a safe option that enhances remission rates without adding extra risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome]. Mao, JP., Xue, LG., Zhu, YX., et al.[2023]

The FLAG-IDA chemotherapy regimen was administered to seven children with refractory acute myeloid leukemia (AML), and while it was tolerable with no early deaths, the efficacy remains uncertain due to high relapse rates and limited patient numbers.

Hematological toxicity was common among patients, with one case of severe non-hematological toxicity (bacterial meningitis), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia. Nakayama, H., Tomizawa, D., Tanaka, S., et al.[2018]

In a study of 21 patients with refractory or recurrent acute myeloid leukemia (R/R AML), the triple therapy of decitabine, idarubicin, and cytarabine (D-IA) resulted in a 47.6% complete remission rate after one treatment cycle, indicating significant efficacy.

The treatment was generally well tolerated, with no treatment-related mortalities reported, although common side effects included hematological toxicity and infections, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia. Zhao, H., Xu, L., Yang, Y., et al.[2018]

Decitabine is an effective hypomethylating agent for treating acute myeloid leukemia (AML), significantly improving overall survival and response rates compared to standard care, based on results from the phase 3 DACO-016 trial with adult patients who are not eligible for standard chemotherapy.

The treatment is generally well tolerated and remains effective even in patients with adverse-risk karyotypes or TP53 mutations, making it a valuable option for those unfit for more intensive therapies, with potential for future combination treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. Santini, V., Lübbert, M., Wierzbowska, A., et al.[2022]

In a phase I trial involving 37 pediatric patients with relapsed/refractory acute myeloid leukemia (R/R AML), the combination of decitabine, vorinostat, and FLAG chemotherapy showed a promising overall response rate of 54%, with 16 patients achieving complete response (CR).

The treatment was well-tolerated with no dose-limiting toxicities, and among those who responded, 90% achieved minimal residual disease (MRD) negativity, leading to a significantly higher two-year overall survival rate of 75.6% for MRD-negative patients compared to 17.9% for those with residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium. Pommert, L., Schafer, ES., Malvar, J., et al.[2023]

In a study of 45 patients with high-risk myeloid malignancies, the FLAG-IDA treatment regimen resulted in a 53% complete remission rate, demonstrating its effectiveness against these aggressive cancers.

Despite some serious side effects, including pulmonary toxicity and mucositis, the FLAG-IDA regimen showed an overall survival rate of 40% at 12 months, indicating it has an acceptable safety profile for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. de la Rubia, J., Regadera, A., Martín, G., et al.[2019]

In a study of 42 adult patients with relapsed or refractory acute myeloid leukemia (AML) treated with the FLAG ± Ida chemotherapy regimen, the complete remission (CR) rate was 47.6%, which aligns with historical rates of 52% to 63%.

The median overall survival (OS) for patients achieving CR was not reached, with an estimated 48-month survival rate of 56%, indicating that FLAG ± Ida remains an effective salvage treatment for R/R AML, despite common adverse effects like pancytopenia and infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Analysis of Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia Treated with FLAG at a Comprehensive Cancer Center. Tenold, ME., Moskoff, BN., Krishnan, R., et al.[2022]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-01992

Chemotherapy (Decitabine in Combination with FLAG-Ida) ... This phase I/II trial studies the safety, side effects, and best dose of decitabine in combination with fludarabine, cytarabine, filgrastim, and idarubicin ...

2. withpower.com withpower.com/trial/phase-2-acute-undifferentiated-leukemia-aul-8-2025-87a27

Decitabine + FLAG-Ida for Myeloid Malignancies This phase I/II trial studies the safety, side effects, and best dose of decitabine in combination with fludarabine, cytarabine, filgrastim, and idarubicin ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03164057

NCT03164057 | A Trial of Epigenetic Priming in Patients ... The overall aim of this study is to determine if epigenetic priming with a DNA methyltransferase inhibitor (DMTi) prior to chemotherapy blocks is tolerable ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6718585/

A favorable inductive remission rate for decitabine ... In conclusion, DAC+IA is therefore offered as a new induction choice for newly diagnosed AML patients with features of MDS, aged <60 years old, especially in ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00943

Fludarabine, Cytarabine, Granulocyte Colony-Stimulating ... The combination of GO with FLAG-Ida increased myelosuppression but also improved event-free survival (EFS) compared with DA + GO. There was ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06928662

Chemotherapy (Decitabine in Combination With FLAG-Ida) ... This phase I/II trial studies the safety, side effects, and best dose of decitabine in combination with fludarabine, cytarabine, filgrastim, and idarubicin ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212623006331

Safety and efficacy of FLAG-Ida-based therapy combined ... FLAG-Ida-VEN seems tolerable and effective in ND and R/R AML. · Rates of neutropenic fever, bacteremia, pneumonia & IFI were 44–55 %, 24–48 %, 12–30 % & 11–36 %, ...

8. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473646

Moving Away From Standard Induction in Newly ... There are no randomized data showing that FLAG-IDA has improved outcomes compared with 7+3 induction chemotherapy. Many patients who are ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11983621/

Case Report: Decitabine and venetoclax sequentially followed ... The prognosis of MECOMr AML is poor, with a 5-year overall survival (OS) rate of less than 10%. This is mostly attributable to the low efficacy ...