Combination Therapy for Pediatric Acute Myeloid Leukemia

Overseen By Alexandra M Stevens, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Joanna Yi

Must be taking: Cytarabine, Daunorubicin, Gemtuzumab

Disqualifiers: Fanconi anemia, Schwachman Diamond, others

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

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for pediatric acute myeloid leukemia (AML), a type of blood cancer, by testing various chemotherapy combinations, including Idarubicin Hydrochloride and Venetoclax. The goal is to determine if these regimens can help patients at intermediate and high risk of relapse live longer without long-term side effects. Eligible participants should have been recently diagnosed with AML or myeloid sarcoma and have undergone one induction cycle of chemotherapy. As an Early Phase 1 trial, this research aims to understand how these treatments work in children, offering a chance to be among the first to receive potentially groundbreaking therapies.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether 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?

Research has shown that using venetoclax with idarubicin is safe and effective for children with acute myeloid leukemia (AML). Studies have found that this combination can significantly shrink or even eliminate the cancer, improving survival chances. Most patients have tolerated this treatment well, even alongside strong chemotherapy.

Another study found that venetoclax, when combined with standard chemotherapy, is safe and effective for children with AML. Even in cases where the cancer recurred or was difficult to treat, children responded well. Among the first 20 children treated with venetoclax and chemotherapy, safety results were positive.

Overall, these findings suggest that the treatment under study is generally safe and well-tolerated for children with AML. However, as this trial is still in the early stages, ongoing research will continue to monitor side effects and efficacy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for pediatric acute myeloid leukemia (AML) involve standard chemotherapy drugs like daunorubicin and cytarabine. However, researchers are excited about the use of idarubicin hydrochloride (Ida-FLA) in combination therapies because it offers a unique approach. Idarubicin is an anthracycline similar to daunorubicin but is more potent, potentially allowing for more effective treatment with lower doses. This combination therapy is uniquely tailored to different risk groups, providing intensified chemotherapy for intermediate and high-risk patients and the possibility of hematopoietic stem cell transplantation, which aims to improve outcomes by precisely targeting the cancer cells. This personalized and powerful approach is what makes these treatments stand out.

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

This trial will evaluate different treatment combinations for pediatric acute myeloid leukemia (AML). Studies have shown that the combination of venetoclax, idarubicin, and cytarabine (VIA), administered to participants in the high-risk arm of this trial, is effective and relatively safe for children with newly diagnosed AML. This treatment helps achieve deep remission, where the cancer is not detectable, and improves survival rates. Research indicates that the overall survival rate can reach 74.4% for patients who receive a stem cell transplant after starting venetoclax. Meanwhile, the combination of idarubicin with fludarabine and cytarabine (Ida-FLA) is under study in both the intermediate and high-risk arms to determine if it can further improve treatment outcomes. Overall, these treatment plans aim to increase survival while reducing long-term side effects. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for pediatric patients with newly diagnosed Acute Myeloid Leukemia (AML) who are at intermediate or high risk of relapse. They should be at the end of their first induction cycle to participate. Specific inclusion and exclusion criteria details were not provided, but typically these would cover age range, health status, and other medical conditions.

Inclusion Criteria

I have AML and meet specific initial diagnosis criteria.

I have a confirmed diagnosis of myeloid sarcoma, with or without bone marrow involvement.

A complete blood count documenting the presence of at least 1,000/µL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed

Exclusion Criteria

I have a genetic condition that increases risk with AML therapy.

I do not have any other cancer types or specific leukemia conditions.

I am not pregnant, breastfeeding, or planning to become pregnant without using effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction 2

Participants receive Ida-FLA (idarubicin+fludarabine/cytarabine) as the second cycle of chemotherapy

4-8 weeks

Multiple visits for chemotherapy administration and monitoring

Intensification 1

High-risk patients receive VIA (venetoclax+idarubicin+cytarabine) as the third cycle of chemotherapy

4-8 weeks

Multiple visits for chemotherapy administration and monitoring

Intensification 2

Intermediate-risk patients receive VIA (venetoclax+idarubicin+cytarabine) as the fourth cycle of chemotherapy

4-8 weeks

Multiple visits for chemotherapy administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Regular follow-up visits for monitoring and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Idarubicin Hydrochloride
• Venetoclax

Trial Overview The study tests substituting two chemotherapy cycles ('Ida-FLA' and 'VIA') into standard AML treatment to see if they can improve survival rates while reducing long-term complications. The effectiveness and side effects will be monitored over three years, along with optional patient surveys and biological sample testing.

How Is the Trial Designed?

Group I: Low risk (LR) Experimental Treatment 1 Intervention

Low risk pediatric AML patients will receive standard of care chemotherapy but have the option to participate in correlative studies

Group II: Intermediate Risk (IR) AML Experimental Treatment 7 Interventions

Patients will receive Ida-FLA as Induction 2, cytarabine/etoposide ("AE") as Intensification 1, VIA as Intensification 2, and Capizzi AraC as intensification 3.

Group III: High risk (HR) AML Experimental Treatment 5 Interventions

Patients will receive Ida-FLA as Induction 2 and VIA as Intensification 1. These patients will then proceed on to a hematopoietic stem cell transplantation if an appropriate donor is found, otherwise will receive 2 more cycles of chemotherapy following the IR regimen.

Who Is Running the Clinical Trial?

Joanna Yi

Lead Sponsor

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40293351/

Venetoclax plus Modified-Intensity Idarubicin and ... VIA regimen is highly effective and relatively safe in children with ND-AML, with deep remission and favorable survival outcomes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05955261

NCT05955261 | A Study of Venetoclax in Combination ... This is a phase 2 study to test the hypothesis that venetoclax in combination with standard chemotherapy will be tolerable and active in pediatric patients ...

3. mdpi.com mdpi.com/2072-6694/16/1/73

Venetoclax: A Game Changer in the Treatment of Younger ... The estimated 30-month OS after the start of VEN was 29.9% for the whole cohort and 74.4% for patients undergoing HSCT. According to this data, ...

4. thelancet.com thelancet.com/cms/10.1016/S1470-2045(20)30060-7/attachment/f898b55f-2d6e-468b-879c-622322c097bd/mmc1.pdf

Supplementary appendix The secondary objective of this study is to estimate the overall response rate to the combination of venetoclax and chemotherapy in pediatric ...

5. stjude.org stjude.org/care-treatment/clinical-trials/venaml-acute-myeloid-leukemia.html

VENAML: Chemotherapy Combined with Venetoclax in ... Only 50–70% of children with newly diagnosed acute myeloid leukemia (AML) can be cured, and the outcomes for children with refractory (hard to treat) or ...