Combination Therapy for Acute Myeloid Leukemia

Overseen By Filippo Milano, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Anti-leukemia agents

Disqualifiers: CNS disease, Cardiac disease, Pulmonary disease, 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: 31

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to determine their safety and effectiveness in treating certain serious blood cancers, such as acute myeloid leukemia (AML), in older adults. It combines intense chemotherapy (FLAG-Ida) with Total-Body Irradiation and a donor stem cell transplant to target cancer cells while reducing the duration of low blood cell counts, which can lead to infections and other complications. The trial seeks participants aged 60 and older, or younger individuals unsuitable for more intense treatments, who have recently been diagnosed with high-risk blood cancers and are interested in a stem cell transplant. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that treatment with any other approved or investigational anti-leukemia agents is not allowed, so you may need to discuss your current medications with the trial team.

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

Research has shown that the FLAG-Ida chemotherapy treatment, which includes fludarabine, cytarabine, idarubicin, and G-CSF, is generally well-tolerated by patients. In studies with similar treatments, common side effects included neutropenic fever in 44–55% of cases, bacterial infections in 24–48%, pneumonia in 12–30%, and fungal infections in 11–36%. These side effects are expected and managed with supportive care.

Total body irradiation (TBI), part of this trial, effectively prepares the body for a stem cell transplant. However, it can cause serious side effects, such as infections and low blood cell counts, which are typical for this kind of treatment.

Overall, while these treatments carry risks, they aim to improve outcomes for patients with high-risk leukemia. Prospective participants should discuss potential side effects with healthcare providers to understand personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Acute Myeloid Leukemia, which often involve chemotherapy and stem cell transplants, the FLAG-Ida regimen is unique because it combines multiple chemotherapy agents—fludarabine, cytarabine, and idarubicin—with targeted radiation therapy (TBI) before a stem cell transplant. This combination aims to aggressively target cancer cells, potentially improving outcomes by using a multi-pronged attack. Researchers are excited because this approach may enhance the effectiveness of the transplant and reduce the risk of relapse, offering hope for better survival rates in patients with this challenging condition.

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

Research has shown that the FLAG-Ida treatment, which includes fludarabine, cytarabine, and idarubicin, holds promise for treating acute myeloid leukemia (AML). Studies have found that this combination helps patients achieve remission more often and recover faster. In this trial, participants will receive the FLAG-Ida treatment alongside total body irradiation (TBI) and hematopoietic cell transplantation (HCT). Using TBI in this treatment has been linked to lower chances of cancer returning compared to treatments without TBI. This suggests that combining these treatments may lead to better outcomes for older adults with high-risk AML. ^{1 2 3 6 7}

Who Is on the Research Team?

Filippo Milano, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for adults aged 60 and older with newly diagnosed adverse-risk acute myeloid leukemia or other high-grade myeloid cancers. Participants must be eligible for donor hematopoietic cell transplant (HCT) and able to undergo the procedures involved in the study.

Inclusion Criteria

Participants must have an available caregiver

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so on my behalf.

I have a new, untreated high-risk blood cancer.

Exclusion Criteria

I do not have severe heart failure, uncontrolled heart rhythm problems, or a history that would prevent me from undergoing a stem cell transplant.

I have an active brain or spinal cord disease.

Participants with psychiatric illness/social situations limiting compliance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemotherapy

Participants receive FLAG-Ida chemotherapy regimen including fludarabine, cytarabine, and idarubicin

5 days

Daily visits for chemotherapy administration

Radiation

Participants undergo reduced-intensity total body irradiation (TBI)

1-2 days

1-2 visits for radiation therapy

Transplantation

Participants undergo allogeneic hematopoietic cell transplant (HCT)

1 day

1 visit for transplantation

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Follow-up visits at days 28, 56, 80, months 3, 6, and years 1, 2

What Are the Treatments Tested in This Trial?

Interventions

• FLAG-Ida
• Total-Body Irradiation

Trial Overview The trial tests a combination chemotherapy regimen (FLAG-Ida), followed by reduced-intensity total body radiation therapy (TBI) and donor HCT. The aim is to treat cancer effectively while reducing the period of low blood cell counts, which can lead to infections and chronic side effects.

How Is the Trial Designed?

Group I: Treatment (FLAG-Ida, TBI, HCT) Experimental Treatment 13 Interventions

Patients receive granulocyte colony-stimulating factor SC QD on days -9 to -4 or days -7 to -4 as clinically indicated, fludarabine IV over 30 minutes QD on days -8 to -4, cytarabine IV over 2 hours QD on days -8 to -4, and idarubicin IV over 60 minutes QD on days -8 to -6. Patients undergo TBI QD on days -1 and 0 or BID on day 0. Patients then undergo allogeneic HCT with unmodified peripheral blood stem cells IV on day 0 or 1 day after TBI as clinically indicated. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MUGA or ECHO during screening and as clinically indicated, undergo bone marrow biopsy and/or aspiration throughout the study and blood sample collection during follow up.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Citations

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

Fludarabine, Cytarabine, Granulocyte Colony-Stimulating ... Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212620300230

Improved Post remission survival of non- favorable risk ... Our data shows that FLAG+/- Ida results in higher remission rates after one course of treatment, shorter time to count recovery, faster time to transplant and ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT194203

Idarubicin and cytarabine with clofarabine or fludarabine in ... Idarubicin and cytarabine with clofarabine or fludarabine in adults with newly diagnosed acute myeloid leukemia: Updated results of a randomized phase II study.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11012572/

FLAG/FLAG-Ida Regimen in Secondary and Relapsed ... The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with ...

5. haematologica.org haematologica.org/article/view/haematol.2023.282912

Fludarabine, cytarabine, and idarubicin with or without ... In R/R AML, 67% of patients treated with FLAG-IDA with venetoclax (FLAVIDA) achieved a CRc and 46% transitioned to alloHCT. Median OS in R/R AML ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2891/533180/Survival-Analysis-of-Gimema-AML1718-a-Safety-Run

Survival Analysis of Gimema AML1718, a Safety Run-in and ... No unexpected long term toxicity or transplant-related toxicity emerged. Predicted 2 years survival seems to favor the adoption of this ...

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 %, ...