Drug Sensitization for Acute Myeloid Leukemia

Not currently recruiting at 1 trial location

Overseen By Meagan Jacoby, M.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must be taking: Cytarabine, Decitabine, Azacitidine, Venetoclax

Must not be taking: Investigational agents

Disqualifiers: Pregnant, HIV, Hepatitis C, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how different chemotherapy drugs can be combined to more effectively treat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), both types of blood cancers. Researchers aim to determine if testing drugs outside the body can predict their effectiveness in patients, particularly when cancer cells resist treatment. The trial includes several treatment plans using drugs like cytarabine, decitabine, azacitidine, and venetoclax, each in specific combinations to identify the most effective one. Individuals with AML or MDS, who have a certain level of cancer cells in their blood and have not received similar drug treatments before, may be suitable candidates. 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 therapy.

Will I have to stop taking my current medications?

The trial requires that you stop any chemotherapy at least 7 days before enrolling, and any prior TKI therapy must be stopped within 3 days of baseline blood collection. You may continue taking hydrea if you meet the blood criteria.

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

Research has shown that the treatments in this trial have been studied before, each yielding different safety results.

For patients receiving cytarabine and idarubicin, studies indicate this combination is generally safe, with 50% to 80% achieving complete remission after treatment. Patients over 60 have demonstrated better safety outcomes with this combination.

Decitabine is well-tolerated with manageable side effects, especially in older patients with acute myeloid leukemia (AML). Real-world data confirm its safety, leading to longer survival and less need for blood transfusions.

Azacitidine, often used for conditions like myelodysplastic syndromes (MDS), is generally well-tolerated. However, reports of serious side effects, including some deaths, exist. Many patients handle the drug well, with most serious issues linked to the disease rather than the treatment.

For those receiving decitabine with venetoclax, research shows this combination is safe and effective for older AML patients. Common side effects include low red and white blood cell counts and nausea.

Lastly, the azacitidine and venetoclax combination has been used safely in hospitals, though reports of serious side effects like severe infections (sepsis) exist. However, overall survival rates and treatment effectiveness have improved with this combination.

These findings suggest that while some risks exist, the treatments are manageable and potentially beneficial for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) because they explore the potential of combining standard chemotherapy drugs with other agents like venetoclax. Unlike traditional approaches that rely solely on chemotherapeutic agents such as cytarabine and idarubicin, these combinations aim to enhance the effectiveness of treatment by adding drugs like venetoclax, which targets specific proteins to induce cancer cell death. Additionally, this trial investigates alternative dosing strategies with drugs like decitabine and azacitidine, potentially offering more tailored treatment regimens. This could lead to improved outcomes and more personalized treatment options for patients with AML and MDS.

What evidence suggests that this trial's treatments could be effective for chemotherapy resistance?

This trial will evaluate different treatment regimens for acute myeloid leukemia (AML). Research has shown that combining cytarabine with idarubicin, which participants in Cohort 1 may receive, effectively treats AML. Studies have found that this combination can help patients live longer compared to some other treatments. For older patients with AML, research indicates that decitabine, tested in Cohort 2, shows a good response rate. Azacitidine, tested in Cohort 3, also appears promising, with evidence suggesting it can help certain AML patients live longer. When combined with venetoclax, as in Cohorts 4 and 5, decitabine or azacitidine become even more effective. These combinations have led to high remission rates, making the cancer undetectable in more than half of the patients treated. ^{6 7 8 9 10}

Who Is on the Research Team?

Meagan Jacoby, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Peripheral blood blasts > 1%

Peripheral white blood cell count > 1,000/µl.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy treatment based on their assigned cohort, including cytarabine/idarubicin, decitabine, azacitidine, and combinations with venetoclax

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bone marrow aspirate
• Buccal swab
• Peripheral blood draw

How Is the Trial Designed?

Group I: Cohort 5 Experimental Treatment 0 Interventions

* Patients treated with azacitidine + venetoclax * Patients will receive azacitidine 75 mg/m2/day as a 1-hour infusion or by subcutaneous injection on consecutive Days 1-7 or on day 1-5 and 8-9 (per treating physician discretion) of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter.

Group II: Cohort 4 Experimental Treatment 3 Interventions

* Patients treated with decitabine + venetoclax * Patients will receive decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 (per treating physician discretion) of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter.

Group III: Cohort 3 Experimental Treatment 3 Interventions

* Patients treated with azacitidine * Patients will receive azacitidine 75 mg/m2/day as a subcutaneous injection on Days 1-7 or on day 1-5 and 8-9 (per treating physician discretion) of each 28-day cycle

Group IV: Cohort 2 Experimental Treatment 3 Interventions

* Patients treated with decitabine * Patients will receive decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 (per treating physician discretion) of each 28-day cycle.

Group V: Cohort 1 Experimental Treatment 3 Interventions

* Patients treated with cytarabine/idarubicin induction therapy * Patients will receive a standard cytarabine/idarubicin induction, which includes cytarabine 200 mg/m2 CIVI in 0.9% normal saline over 24 hours for 7 consecutive days (Days 1-7) and idarubicin 12 mg/m2 per day in 0.9% normal saline over 15-30 minutes for 3 consecutive days (Days 1-3). Other standard cytarabine-based induction protocols are allowed (e.g. cytarabine/daunorubicin or Vyxeos).

Group VI: Cohort 0 Experimental Treatment 3 Interventions

-A technical run-in of 5 patients with any of the following: * Standard cytarabine/idarubicin induction, includes cytarabine 200 mg/m2 CIVI in 0.9% normal saline over 24 hours for 7 consecutive days (Days 1-7) \& idarubicin 12 mg/m2 per day for 3 consecutive days (Days 1-3). Other standard cytarabine-based induction protocols are allowed * Decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 of each 28-day cycle. * Azacitidine 75 mg/m2/day as a subcutaneous injection on Days 1-7 or on day 1-5 and 8-9 of each 28-day cycle * Decitabine 20 mg/m2/day as a 1-hour infusion on consecutive Days 1-5 or 1-10 of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter. * Azacitidine 75 mg/m2/day as a 1-hour infusion or by subcutaneous injection on consecutive Days 1-7 or on day 1-5 and 8-9 of each 28-day cycle. Patients will receive venetoclax PO 100 mg on Day 1, 200 mg on Day 2, and 400 mg daily thereafter.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Notable Labs

Industry Sponsor

Trials

2

Recruited

200+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9793740/

Clinical Utility of Azacitidine in the Management of Acute ... The data suggest that oral AZA maintenance is an effective maintenance strategy to prolong survival in high-risk as well as favorable-risk AML ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2425/531542/Real-World-Treatment-Patterns-and-Outcomes-with

Real-World Treatment Patterns and Outcomes with Oral ... At 12 mo, estimated OS and rwRFS rates from Oral-AZA initiation were 88.2% (standard error [SE], 2.3) and 85.5% (SE, 2.5), respectively. Median ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213048916300486

Clinical outcomes of AML patients treated with Azacitidine ... Median OS was 10.6 months in those receiving AZA as 1st line. Response (overall response rate 44%) had a significant impact on overall survival (p=<0.0001).

4. 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 ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2948932/

Safety & Efficacy of Azacitidine in Myelodysplastic Syndromes Patients treated with azacitidine had median overall survival of 24.5 months, while patients receiving conventional care had a median overall survival of 15.0 ...

7. hematologyadvisor.com hematologyadvisor.com/news/azacitidine-myelodysplastic-syndrome-mds-adverse-events-safety-concerns/

New Adverse Events Highlight Safety Concerns With ... Most AEs (95.78%) were classified as serious, and 40.87% resulted in death. Health professionals submitted nearly 90% of the reports, with the ...

8. 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 ... Adverse events reflected known safety profiles for venetoclax and azacitidine, including constipation (53.3%), nausea (49.5%), neutropenia (48.6 ...

9. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1555838/full

The real-world analysis of adverse events with azacitidine Azacitidine was generally well tolerated in patients with MDS and AML. Most deaths or adverse events leading to drug interruption were attributed to the disease ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/050974s034lbl.pdf

VIDAZA (azacitidine - accessdata.fda.gov The safety of VIDAZA was evaluated in pediatric patients ... Survival data for patients 65 years and older were consistent with overall survival results.