Azacitidine + Chemotherapy for Acute Lymphoblastic Leukemia

No longer recruiting at 190 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Down syndrome, Secondary B-ALL, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining azacitidine, a chemotherapy drug, with various other chemotherapy drugs in infants with acute lymphoblastic leukemia involving a specific genetic change called KMT2A rearrangement. Researchers aim to determine if using multiple drugs together can kill more cancer cells and identify any side effects. Eligible infants have newly diagnosed B lymphoblastic leukemia or a similar condition, have not received other cancer treatments besides steroids or specific chemotherapy, and do not have conditions like Down syndrome. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that prior cytotoxic chemotherapy is not allowed, except for certain steroids and specific chemotherapy drugs given directly into the spinal fluid.

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

Research has shown that azacitidine is safe and well-tolerated in infants with acute lymphoblastic leukemia, particularly those with a specific gene change called KMT2A rearrangement. One study found that azacitidine reduced DNA methylation, which affects gene function, in these infants without causing significant harm. Previous patients have demonstrated that azacitidine can be safely combined with chemotherapy for this condition.

The other drugs in the trial, such as methotrexate, daunorubicin, and cytarabine, are standard chemotherapy medications. They have known side effects, which are usually managed during treatment. By using a combination of drugs, doctors aim to kill more cancer cells while carefully monitoring for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard chemotherapy regimens for acute lymphoblastic leukemia (ALL), which typically focus on directly killing cancer cells, the addition of azacitidine offers a new approach by targeting the epigenetic changes in cancer cells. Azacitidine works by modifying the DNA of leukemia cells, potentially reactivating genes that suppress tumor growth. This unique mechanism can make cancer cells more sensitive to traditional chemotherapy, potentially improving outcomes. Researchers are excited because this combination might enhance the effectiveness of existing treatments, offering hope for better remission rates in patients with ALL.

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

Research has shown that azacitidine, which participants in this trial will receive alongside chemotherapy, holds promise for treating acute lymphoblastic leukemia, particularly in infants with a specific genetic change called KMT2A gene rearrangement. Studies have found that azacitidine can be safely and effectively combined with chemotherapy, aiding patients in achieving complete remission, where no signs of cancer are detected. Infants with this genetic condition have experienced positive outcomes. While azacitidine alone has demonstrated a complete response rate of about 15–20% in some studies, it appears to enhance leukemia cells' response to chemotherapy, making the overall treatment more effective. This combination aims to halt the growth, division, or spread of cancer cells, thereby increasing the chances of remission. ^{3 6 7 8 9}

Who Is on the Research Team?

Rishi S Kotecha

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for infants over 36 weeks gestational age with newly diagnosed B lymphoblastic leukemia or acute leukemia of ambiguous lineage, without Down syndrome or prior malignancies treated with cytotoxic chemotherapy. They must not have received previous cancer treatments, except certain steroids and intrathecal drugs.

Inclusion Criteria

My baby was born after 36 weeks of pregnancy.

My CNS status was checked before any major cancer treatment, except steroids.

My leukemia is newly diagnosed and falls under B lymphoblastic or mixed phenotype.

Exclusion Criteria

I haven't had chemotherapy for my current B-ALL or any other cancer, except for steroids or specific spinal treatments.

My B-ALL developed after chemotherapy for another cancer.

My leukemia does not have the KMT2A rearrangement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Patients receive a combination of chemotherapy drugs including methotrexate, prednisolone, daunorubicin hydrochloride, cytarabine, dexamethasone, vincristine sulfate, pegaspargase, and hydrocortisone sodium succinate.

5 weeks

Azacitidine Block I

Patients receive azacitidine IV over 10-40 minutes daily for 5 days.

1 week

Consolidation

Patients receive cyclophosphamide, mercaptopurine, cytarabine, methotrexate, and hydrocortisone sodium succinate.

6 weeks

Azacitidine Block II

Patients receive azacitidine as in Azacitidine Block I.

1 week

Interim Maintenance

Patients receive mercaptopurine, methotrexate, leucovorin calcium, hydrocortisone sodium succinate, cytarabine, and pegaspargase.

4 weeks

Azacitidine Block III

Patients receive azacitidine as in Azacitidine Block I.

1 week

Delayed Intensification Part I

Patients receive pegaspargase, dexamethasone, thioguanine, vincristine sulfate, daunorubicin hydrochloride, cytarabine, and hydrocortisone sodium succinate.

4 weeks

Azacitidine Block IV

Patients receive azacitidine as in Azacitidine Block I.

1 week

Delayed Intensification Part II

Patients receive thioguanine, cyclophosphamide, and cytarabine.

2 weeks

Maintenance

Patients receive mercaptopurine, methotrexate, hydrocortisone sodium succinate, and cytarabine. Cycles repeat every 84 days for 2 years.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Cyclophosphamide
• Cytarabine
• Daunorubicin
• Daunorubicin Hydrochloride
• Dexamethasone
• Hydrocortisone Sodium Succinate
• Laboratory Biomarker Analysis
• Leucovorin
• Leucovorin Calcium
• Mercaptopurine
• Methotrexate
• Pegaspargase
• Pharmacological Study
• Prednisolone
• Thioguanine
• Vincristine
• Vincristine Sulfate

Trial Overview The trial tests the side effects of azacitidine combined with other chemotherapy drugs in treating infant leukemia with KMT2A gene rearrangement. It aims to see if using multiple drugs can more effectively kill cancer cells by working together in different ways.

How Is the Trial Designed?

Group I: Treatment (azacitidine, combination chemotherapy) Experimental Treatment 21 Interventions

See Detailed Description

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2817034/

5-azacitidine prolongs overall survival in patients with ... Although all trials showed complete and partial response rates of about 15–20%, results regarding time to leukemic transformation or death and overall survival ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609799/

Azacitidine as epigenetic priming for chemotherapy is safe ... Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265022011880

Acute Lymphoblastic Leukemia ALL-220 Azacitidine in ... The median duration of maintenance treatment was 12.75 months (range, 9.5–23.5 months). All patients remain in continuous complete remission with undetectable ...

4. haematologica.org haematologica.org/article/view/haematol.2024.285158

Azacitidine as epigenetic priming for chemotherapy is safe ... Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0145212613001112

Azacitidine results in comparable outcome in newly ... We analyzed 55 newly diagnosed AML patients, treated with azacitidine. The overall response rate was 42%. Median overall survival (OS) was 12.3 months. We ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38867582/

Children's Oncology Group trial AALL15P1 - PubMed - NIH Azacitidine is safe and results in decreased DNA methylation of peripheral blood mononuclear cells in infants with KMT2A-r ALL.

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

Safety and efficacy of azacitidine in myelodysplastic ... A subset analysis of the AZA-001 trial in patients older than 75 years demonstrated higher overall survival rates at 2 years in the azacitidine group (55%) than ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2024.2390572

Long-term exposure and response to azacitidine for post- ... Adult T-cell acute lymphoblastic leukemia has a poor outcome after relapse. Because the subtype of early T-cell precursor displays ...

9. ashpublications.org ashpublications.org/blood/article/110/7/2302/103627/Safety-and-clinical-activity-of-the-combination-of

Safety and clinical activity of the combination of 5-azacytidine ... We conducted a phase 1/2 study of the combination of 5-azacitidine (5-AZA), valproic acid (VPA), and ATRA in patients with acute myeloid leukemia or high-risk ...