Treatment Intensity for Acute Myeloid Leukemia

Overseen By Jacob Appelbaum, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Fred Hutchinson Cancer Center

Must not be taking: Cytarabine, Anthracycline, Hypomethylating agents, Venetoclax

Disqualifiers: Cardiovascular disability, Uncontrolled infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adults with acute myeloid leukemia (AML) or similar conditions are open to allowing a computer program to decide their chemotherapy intensity. The study compares higher-intensity and lower-intensity chemotherapy to identify which is more effective for individuals who may not tolerate strong treatments. Participants will be divided into groups based on whether the computer or they themselves choose the treatment intensity. Those with AML or myeloid neoplasms, who experience significant symptoms and have concerns about treatment side effects, might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to explore innovative treatment decision-making methods that could improve patient outcomes.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study found that patients with acute myeloid leukemia (AML) who received more intense chemotherapy at specialized centers lived longer. They had a median survival of 31 months, compared to 18 months for those treated at non-specialized centers. However, more intense treatments can also cause more side effects.

Research shows that less intense chemotherapy can be safer for older or less fit patients. Specifically, one study found that about 10% of patients experienced serious side effects, indicating it might be a gentler option for those unable to handle intense treatment.

Both treatment options have their pros and cons, so personal health and preferences should guide the decision-making process. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different intensities of chemotherapy might impact patients with Acute Myeloid Leukemia (AML). Current treatments often involve the 7+3 regimen, a standard higher-intensity chemotherapy. This trial compares higher-intensity options with lower-intensity alternatives, potentially less severe than the 5+2 regimen. The unique aspect is that it also considers patient and physician preference, which could lead to more personalized treatment plans. By studying these variations, researchers hope to find the best balance between effectiveness and quality of life for patients.

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

This trial will compare higher-intensity chemotherapy with lower-intensity chemotherapy for patients with acute myeloid leukemia (AML). Studies have shown that intensive chemotherapy can lead to better outcomes for AML patients. For instance, recent evidence suggests that about 60% of younger, healthier patients achieve long-term remission. Outcomes improve further when treatment occurs at specialized centers.

Conversely, research indicates that less intense chemotherapy can be effective, particularly for older or less healthy patients. One study found that combining venetoclax and azacitidine resulted in significantly better outcomes than azacitidine alone, with higher complete remission rates. Another study reported high success rates with these less intense treatments, with event-free survival rates reaching up to 89%. Participants in this trial will either be randomized or choose between higher-intensity and lower-intensity therapy options. ^{4 6 7 8 9}

Who Is on the Research Team?

Jacob Appelbaum, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for less fit adults with acute myeloid leukemia (AML) or myeloid neoplasms who are open to letting a computer decide their treatment intensity. It's not clear if they should get lower-intensity 'palliative' therapy or higher-intensity 'curative' chemotherapy.

Inclusion Criteria

The presence of one or more of the following criteria for 'unfitness'. (Patients without respiratory symptoms at rest are eligible and should only complete spirometry/diffusion capacity of the lung for carbon monoxide [DLCO] measurements as clinically indicated):

Total bilirubin ≤ 3 x ULN unless judged due to leukemic organ involvement, Gilbert's syndrome, or hemolysis

Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 4 weeks after the last dose of study drug

Exclusion Criteria

Known hypersensitivity to cytarabine, anthracycline, hypomethylating agents, or venetoclax

Active pregnancy or breast feeding

I have a health condition that may limit my life to less than a year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either higher-intensity or lower-intensity chemotherapy based on randomization or choice, with blood sample collection and bone marrow assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Higher-Intensity Chemotherapy
• Lower-Intensity Chemotherapy

Trial Overview The study tests whether patients will accept random assignment to either lower- or higher-intensity chemotherapy, using a computer program. The goal is to find the best treatment approach for those traditionally considered unfit for intensive therapy.

How Is the Trial Designed?

Group I: Arm II (randomized lower-intensity therapy) Experimental Treatment 4 Interventions

Patients receive SOC or investigational lower-intensity therapy on a subsequent treatment trial that is less intense than 5+2 regimen at the discretion of the treating physician on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Group II: Arm I (randomized higher-intensity therapy) Experimental Treatment 4 Interventions

Patients receive SOC or investigational higher-intensity therapy on a subsequent treatment trial that is at least as intense as 7+3 regimen at the discretion of the treating physician on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Group III: Arm III (patient choice higher-intensity therapy) Active Control 4 Interventions

Patients receive SOC or investigational higher-intensity therapy on a subsequent treatment trial that is at least as intense as 7+3 regimen according to physician/patient preference on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Group IV: Arm IV (patient choice lower-intensity therapy) Active Control 4 Interventions

Patients receive SOC or investigational lower-intensity therapy on a subsequent treatment trial that is less intense than 5+2 regimen according to physician/patient preference on study. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and bone marrow assessments on study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12050940/

Outcomes with intensive treatment for acute myeloid ... Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcomes of patients with acute myeloid leukemia (AML).

2. ashpublications.org ashpublications.org/hematology/article/2023/1/175/506401/Improving-long-term-outcomes-with-intensive

Improving long-term outcomes with intensive induction ... Recent data from clinical trials in younger fit AML patients across genetic subgroups show long-term remission rates around 60%, whereas 50% ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X25000335

Navigating acute myeloid leukemia towards better outcomes [83,84] Estimated 24-month overall survival rates were 37.5 % versus 16.9 % with venetoclax-azacitidine and placebo-azacitidine, respectively. [84] Rates of ...

4. chi.scholasticahq.com chi.scholasticahq.com/article/124273

Determinants of Outcomes for Acute Myeloid Leukemia ... For AML patients treated with high intensity chemotherapy induction, initial management at a specialized center produced superior survival.

5. haematologica.org haematologica.org/article/view/haematol.2020.269134

Dose intensity for induction in acute myeloid leukemia For instance, SEER data for patients with AML aged 65 years and older from 1991-1996 demonstrated that the median survival was 2.4 months with a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11477936/

Determinants of Outcomes for Acute Myeloid Leukemia ... Patients receiving high-intensity induction at specialized centers had improved median survivals of 31 months versus 18 months [P<0.001] at non- ...

7. haematologica.org haematologica.org/article/view/haematol.2024.285805

Outcomes with intensive treatment for acute myeloid ... The median OS time increased significantly from 15.5 months (95% confidence interval [95% CI]: 13.8-17.6) to 37.8 months (95% CI: 31.6-49.2) ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2152265024024479

Clinical Outcomes of Patients With Newly Diagnosed Acute ... The 5-year OS rate in the entire cohort was 30 % (35 % in patients <60 years and 16 % if ≥60 years), with 92 % of deaths attributed to AML-related complications ...

9. ashpublications.org ashpublications.org/blood/article/141/1/5/493905/Treatment-intensity-in-AML-a-double-edged-sword

Treatment intensity in AML: a double-edged sword | Blood For AML, however, improving cure rates have lagged substantially behind those of ALL, requiring more intensive treatments, frequently including ...