Fludarabine + Cytarabine + Idarubicin + Venetoclax for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: BCL-2 inhibitors, CYP3A4 inducers

Disqualifiers: Active malignancy, CNS involvement, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to treat acute myeloid leukemia (AML), a cancer that begins in the blood and bone marrow. Researchers aim to determine if adding venetoclax to a standard chemotherapy mix more effectively controls the disease. Participants will receive either the new combination or the standard treatment. The trial seeks volunteers recently diagnosed with AML or a similar condition who have not yet received treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you must stop all current medications, but you cannot use strong or moderate CYP3A4 inducers or inhibitors or P-gp inhibitors within 2 days before starting venetoclax. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

A previous study found that the combination of fludarabine, cytarabine, idarubicin, and venetoclax led to a high rate of complete response, with many patients achieving remission and generally tolerating the treatment well. Most patients experienced remission with only mild side effects, though some had a longer recovery time for their blood cells during follow-up treatment.

The combination of cytarabine and daunorubicin is a common chemotherapy treatment for acute myeloid leukemia (AML). These drugs can cause side effects like low blood cell counts, but these effects are usually predictable and manageable.

Both treatment combinations have been used in AML patients before, and evidence suggests they can be safe. However, like all treatments, they carry some risks, and discussing these with the research team before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine a mix of drugs that might improve outcomes for people with Acute Myeloid Leukemia (AML). Unlike the standard of care, which often uses cytarabine and daunorubicin alone, this new approach adds venetoclax and idarubicin to the mix. Venetoclax is particularly interesting because it targets a protein called BCL-2, which helps cancer cells survive, potentially leading to more effective cancer cell death. This combination could offer a more powerful attack on AML, providing new hope for patients who haven't responded well to existing treatments.

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

Research has shown that a combination of four drugs—fludarabine, cytarabine, idarubicin, and venetoclax—can effectively treat acute myeloid leukemia (AML). In this trial, participants in Arm 1 will receive this combination, which may lead to a complete response, meaning no signs of cancer are found. One study showed that all participants achieved a complete response, even those with challenging genetic profiles. Another study found that 71% of patients were still alive one year after starting treatment. Venetoclax, one of the drugs in this combination, blocks a protein that helps cancer cells survive, potentially enhancing the treatment's effectiveness. These findings suggest that this combination therapy could surpass traditional treatments for AML. Meanwhile, participants in Arm 2 will receive a different regimen of cytarabine and daunorubicin, serving as the active comparator in this trial. ^{1 3 4 5 6}

Who Is on the Research Team?

Curtis A Lachowiez

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome. Participants should be suitable for intensive chemotherapy. Specific eligibility criteria are not provided, but typically include factors like age range, overall health status, and having no other treatments for the conditions.

Inclusion Criteria

I understand this study is experimental and I can give my written consent.

My gender, race, or ethnicity does not exclude me from this trial.

I am fully active or have some restrictions but can still care for myself.

Exclusion Criteria

My leukemia has specific genetic changes.

I haven't had any cancer except for early skin cancer in the last 5 years.

My AML has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive induction therapy with fludarabine, cytarabine, idarubicin, and venetoclax or cytarabine and daunorubicin to achieve remission

4 weeks

Multiple visits for IV administration

Consolidation

Patients receive consolidation therapy to eliminate remaining cancer cells, with cycles repeating every 28 days

24 weeks

Multiple visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Fludarabine
• Idarubicin
• Venetoclax

Trial Overview The study compares two AML treatments: one combines fludarabine, cytarabine, idarubicin, and venetoclax; the other uses cytarabine and daunorubicin followed by consolidation with cytarabine alone. It aims to determine if the first regimen is more effective after initial remission.

How Is the Trial Designed?

Group I: Arm 1 (fludarabine, cytarabine, idarubicin, venetoclax) Experimental Treatment 9 Interventions

See Detailed Description.

Group II: Arm 2 (cytarabine, daunorubicin) Active Control 8 Interventions

INDUCTION: Patients receive cytarabine IV on days 1-7 and daunorubicin IV on days 1-3 of each cycle. Cycles repeat every 28 days for up to 1 cycle in the absence of disease progression or unacceptable toxicity. Patients achieving CR, CRh, CRi, or MLFS after one induction cycle proceed to consolidation. Patients achieving PR after one induction cycle may proceed to consolidation at the investigator's discretion. Patients with ≥ 5% blasts after one induction cycle may receive a second cycle of induction therapy. CONSOLIDATION: Participants receive cytarabine IV over 3 hours BID on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for up to 4 post-induction cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO or MUGA scan during screening and on study as clinically indicated. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772520/

Fludarabine, cytarabine, and idarubicin with or without ... In this study, venetoclax was administered at a dose of 400 mg once daily for a median of 8 days. Three patients (12%) experienced early death within 30 days of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07228273?term=heart+disease

Induction and Consolidation With Fludarabine, Cytarabine ... Giving fludarabine, cytarabine, idarubicin, and venetoclax for induction and consolidation therapy may be more effective in treating AML.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952925001521

Safety run-in and part 1 of GIMEMA AML1718: venetoclax ... With a median follow-up of 20.6 months, 1-year overall survival was 71%, 1-year disease-free survival was 66.2%, and 1-year cumulative incidence ...

4. ashpublications.org ashpublications.org/ashclinicalnews/news/8771/FLAG-IDA-Plus-Venetoclax-Performs-Well-in-Children

FLAG-IDA Plus Venetoclax Performs Well in Children, AYA ... All 12 patients achieved complete response (CR). Nine of 12 patients, including many with poor-risk genotypes, achieved measurable residual ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11978487/

Long term results of venetoclax combined with FLAG-IDA ... The CAVEAT trial investigated the addition of venetoclax to an attenuated 5+2 regimen of cytarabine and idarubicin in older fit ND AML, resulting in a CRc rate ...

6. ashpublications.org ashpublications.org/bloodadvances/article/9/10/2542/535910/Safety-run-in-and-part-1-of-GIMEMA-AML1718

venetoclax combined with FLAI as induction treatment in non ... Key PointsIn non–low-risk AML, the addition of VEN to FLAI induction chemotherapy gives high rate of CR and limited toxicities.