Hypomethylating Agents vs. Intensive Chemotherapy for Acute Myeloid Leukemia

Overseen By Titilayo Olubajo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Hypomethylating agents

Disqualifiers: Pregnancy, Uncontrolled conditions, 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: 5

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two different treatment approaches for individuals newly diagnosed with acute myeloid leukemia (AML), a type of blood cancer. It compares the effectiveness of hypomethylating agents, such as Azacitidine or Decitabine, to standard intensive chemotherapy. Researchers use a new blood test to determine the best follow-up treatments. Suitable candidates for this trial are adults recently diagnosed with AML who can commit to the study schedule. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

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

Research has shown that treatments with azacitidine and decitabine are generally well-tolerated by patients with acute myeloid leukemia (AML). Studies have found that these drugs share similar safety profiles, with common side effects such as nausea, diarrhea, and low blood cell counts. When combined with venetoclax, another medication, they also demonstrated good tolerance without unexpected safety issues.

For patients receiving intensive chemotherapy, typically a combination of cytarabine and anthracycline, side effects can include low blood cell counts, nausea, and weakened immune systems. Although effective, these treatments may also cause temporary hair loss and, in some cases, long-term heart problems.

Both treatment options have been studied in patients with AML, and the side effects are well-documented. Potential trial participants should discuss these findings with their healthcare providers to understand what these side effects might mean for them personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute myeloid leukemia (AML) because they offer potentially less toxic options compared to the intensive chemotherapy that is currently standard. Azacitidine and Decitabine are hypomethylating agents, which work by reactivating genes that suppress tumors, offering a different mechanism than traditional chemotherapy. These agents can be used with Venetoclax, a targeted therapy that inhibits the BCL-2 protein, which can help kill cancer cells more effectively in certain patients. Unlike the intense side effects of Anthracycline and Cytarabine, such as heart issues and severe hair loss, the HMA-based treatments might have a more manageable side effect profile, providing hope for patients who cannot tolerate aggressive chemotherapy.

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

This trial will compare hypomethylating agents with intensive chemotherapy for treating acute myeloid leukemia (AML). Research has shown that certain medications, such as azacitidine and decitabine, can effectively treat AML, particularly for patients unable to undergo intensive chemotherapy. In one study, decitabine helped 36.1% of AML patients respond to treatment. These medications also improved survival rates and the chances of a complete response compared to standard care. When combined with another drug called venetoclax, they have shown promise in further improving survival rates. Participants in the Intensive Chemotherapy Arm will receive treatment with drugs like cytarabine and anthracyclines, which is another common treatment for AML but can have significant side effects. ^{1 6 7 8 9}

Who Is on the Research Team?

Shilpan Shah, MD

Principal Investigator

Houston Methodist Neal Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed acute myeloid leukemia (AML). Participants must consent to the trial and if they are sexually active, agree to use two effective contraception methods. Spanish speakers can join with provided translation services.

Inclusion Criteria

I do not engage in sexual intercourse.

My partner is surgically sterile.

I am 18 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either hypomethylating agent-based therapy or intensive induction chemotherapy based on stratified sampling. Blood samples are collected to assess MRD status.

12 weeks

Blood samples collected ± 5 days before and after 4 and 12 weeks of therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRD status guiding further treatment decisions.

30 months

Consolidation

If MRD is negative, participants proceed with consolidation therapy, which may include HSCT or continuation of the same treatment.

What Are the Treatments Tested in This Trial?

Interventions

• 5hmC Biomarker
• Azacitidine
• Decitabine

Trial Overview The study tests hypomethylating agents (like Azacitidine or Venetoclax) against intensive chemotherapy (Cytarabine plus Anthracycline) in treating AML. It uses a new blood marker, 5hmC, to guide treatment after initial therapy and monitor disease status.

How Is the Trial Designed?

Group I: HMA- Based Treatment Arm Active Control 4 Interventions

Azacitidine or Decitabine with or without Venetoclax (HMA-based treatment): * Venetoclax is a BCL-2 inhibitor FDA Approved for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, decitabine or low-dose cytarabine in. * Decitabine is a nucleoside metabolic inhibitor that is administered as an intravenous infusion over a 1-3 hours. * Azacitidine can be given as a sub-cutaneous injection or intravenously. In AML, the most common adverse reactions (≥30%) in combination with azacitidine or decitabine or low-dose cytarabine were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, peripheral edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, back pain, myalgia, dizziness, cough, oropharyngeal pain, and hypotension.

Group II: Intensive Chemotherapy Arm Active Control 3 Interventions

Cytarabine with Anthracycline (standard intensive induction therapy): * Cytarabine is FDA approved chemotherapy (pyrimidine analog) infusion that is frequently used with other drug such as anthracycline to treat acute myeloid leukemia, acute lymphoblastic leukemia. Common side effects include low counts, immune suppression, nausea, neutropenic fever. * Anthracyclines are chemotherapy infusions which topoisomerase II inhibition. Other than having side effects similar to cytarabine, it may cause weakening of heart pumping function few years later. Both of these medications may cause a temporary loss of hair in some people. After treatment with cytarabine has ended, normal hair growth should return.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9305088/

Prospective comparison of outcomes with azacitidine and ... Comparative results of azacitidine and decitabine from a large prospective phase 3 study in treatment naive patients with acute myeloid leukemia not eligible ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212621000254

Efficacy of 10-day decitabine in acute myeloid leukemia Highlights · Real world outcomes using the 10 day decitabine regimen in AML are lacking. · 10-day decitabine had an ORR of 36.1% in AML in the upfront setting.

3. nature.com nature.com/articles/s41375-025-02730-3

Outcomes of patients treated with venetoclax plus ... The 5-year relative survival of patients with AML is ~32%, and survival rates are dependent on age at diagnosis. Patients <50 years of age have ...

4. ashpublications.org ashpublications.org/bloodadvances/article/4/10/2192/456022/Clinical-outcomes-of-older-patients-with-AML

Clinical outcomes of older patients with AML receiving ... Median survival from diagnosis was 7.1 and 8.2 months (P < .01) for azacitidine- and decitabine-treated patients, respectively. Mortality risk ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.701690/full

A Systematic Review and Network Meta-Analysis The results showed that HMAs improved the OS and CR rate compared with CCR and also increased the incidence of neutropenia, thrombocytopenia, ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212623000255

Comparison between azacitidine and decitabine as front- ... Azacitidine and decitabine have comparable efficacy and toxicity in elderly patients with newly diagnosed acute myeloid leukemia.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6614132/

Real Life Data on Efficacy and Safety of Azacitidine ... AZA treatment was effective in a limited number of patients with acceptable safety profile. Keywords: Azacitidine, Myelodysplastic syndrome, ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2012971

Azacitidine and Venetoclax in Previously Untreated Acute ... Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine ...

9. ashpublications.org ashpublications.org/blood/article/145/11/1126/534406/Efficacy-and-safety-of-venetoclax-plus-azacitidine

Efficacy and safety of venetoclax plus azacitidine for patients ... Key PointsVenetoclax (14 days) + azacitidine regimen was well tolerated in patients with treatment-naive HR MDS, with no unexpected safety ...