What side effects are associated with this type of intervention?

Common treatments for Myeloid Leukemia, such as chemotherapy and targeted therapies, often come with significant side effects. Chemotherapy can cause neutropenia (a decrease in white blood cells), leading to an increased risk of infection, as well as anemia and thrombocytopenia, which can result in fatigue and bleeding issues. Other frequent side effects include gastrointestinal issues like diarrhea and nausea, as well as hair loss and mucositis (inflammation of the mucous membranes). Targeted therapies, while potentially more precise, can also cause side effects such as myelosuppression (bone marrow suppression), liver toxicity, and skin rashes. Balancing efficacy and toxicity remains a critical challenge in the treatment of Myeloid Leukemia.

What prior FDA approvals exist?

FDA-approved treatments for Myeloid Leukemia include hypomethylating agents (HMAs) such as azacitidine and decitabine, which work by stopping cancer cells from dividing and spreading. Venetoclax, an orally available BCL2 inhibitor, is used in combination with other agents like low-dose cytarabine (LoDAC) to enhance efficacy. Enasidenib, approved for relapsed/refractory AML with IDH2 mutations, targets specific genetic abnormalities to inhibit cancer cell growth. These treatments align with the mechanisms being studied in response-based chemotherapy trials.

What other types of research exist?

Promising novel alternatives to traditional chemotherapy for Myeloid Leukemia patients include: 1) Hypomethylating agents (HMAs) such as azacitidine and decitabine, which have shown comparable efficacy and are well-tolerated. 2) Combination therapies like low-dose cytarabine (LoDAC) with venetoclax or glasdegib, which have demonstrated superior outcomes compared to LoDAC monotherapy. 3) Targeted therapies for specific mutations, such as enasidenib for IDH2 mutations and ivosidenib for IDH1 mutations, which offer new therapeutic options for relapsed/refractory AML. These alternatives focus on precision medicine and have the potential to improve patient outcomes.

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Enzyme

Chemotherapy for Acute Myeloid Leukemia in Young Patients with Down Syndrome

Phase 3

Waitlist Available

Led By Jason N Berman

Research Sponsored by Children's Oncology Group

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient has previously untreated de novo AML and meets the criteria for AML with >= 20% bone marrow blasts as set out in the World Health Organization (WHO) Myeloid Neoplasm classification

Patients must have constitutional trisomy 21 (Down syndrome) or trisomy 21 mosaicism (by karyotype or fluorescence in situ hybridization [FISH])

Must not have

Patients with promyelocytic leukemia (French-American-British [FAB] M3)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years from study entry

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial studies a chemotherapy treatment that adjusts based on how well patients respond initially. It targets younger patients with Down syndrome who have certain types of blood cancer. The treatment aims to effectively kill cancer cells while reducing side effects.

Who is the study for?

This trial is for young patients with Down syndrome who have newly diagnosed acute myeloid leukemia or myelodysplastic syndrome. They must not have received any anti-leukemic therapy except cytarabine for transient myeloproliferative disease, and they should not have promyelocytic leukemia. Patients need to show a certain percentage of blasts in their bone marrow or blood and meet specific diagnostic criteria.

What is being tested?

The study tests response-based chemotherapy using drugs like Asparaginase Erwinia chrysanthemi, Cytarabine, Daunorubicin Hydrochloride, among others. It aims to categorize patients by risk based on their initial treatment response and adjust subsequent treatments accordingly to reduce side effects while treating the cancer effectively.

What are the potential side effects?

Chemotherapy drugs used may cause side effects such as nausea, vomiting, hair loss, increased risk of infection due to low blood cell counts, bleeding or bruising more easily than normal due to low platelet counts, fatigue from anemia (low red blood cell count), and potential liver problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have a new diagnosis of AML with more than 20% bone marrow blasts.

Select...

I have Down syndrome confirmed by genetic testing.

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I have a blood disorder with low blood counts but not enough to be considered AML.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been diagnosed with a specific type of leukemia (FAB M3).

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years from study entry

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years from study entry

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years from study entry for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event-free survival (EFS)

Other study objectives

Mean duration of hospitalization

Mean length on protocol therapy

Mean time to absolute neutrophil count (ANC) recovery

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B (high risk)Experimental Treatment5 Interventions

INDUCTION II: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours on days 1-4 and mitoxantrone hydrochloride IV over 15-30 minutes on days 3-6. Induction II continues for a minimum of 28 days. INTENSIFICATION I: Patients receive high dose cytarabine IV over 1-3 hours Q12 hours and etoposide IV over 90-120 minutes on days 1-5. Intensification I continues for a minimum of 28 days. INTENSIFICATION II: Patients receive high dose cytarabine IV over 3 hours Q12 hours on days 1, 2, 8, and 9. Patients also receive asparaginase or asparaginase Erwinia chrysanthemi IM or IV over 30 minutes on days 2 and 9. Intensification II continues for a minimum of 28 days.

Group II: Arm A (standard risk)Experimental Treatment5 Interventions

INDUCTION II: Patients receive cytarabine IV continuously over 96 hours, daunorubicin hydrochloride IV over 1-15 minutes, and thioguanine PO BID on days 1-4. Induction II continues for a minimum of 28 days. INDUCTION III: Patients receive cytarabine, daunorubicin hydrochloride, and thioguanine as in Induction II. Induction III continues for a minimum of 28 days. INTENSIFICATION I: Patients receive cytarabine IV continuously over 168 hours on days 1-7 and etoposide IV over 60-120 minutes on days 1-3. Intensification I continues for a minimum of 28 days. INTENSIFICATION II: Patients receive cytarabine and etoposide as in Intensification I. Intensification II continues for a minimum of 28 days. (This arm is closed to accrual and treatment with amendment #4A 01/07/2019)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Asparaginase

2005

Completed Phase 4

~5220

Cytarabine

2016

Completed Phase 3

~3330

Daunorubicin Hydrochloride

2011

Completed Phase 3

~5330

Thioguanine

2012

Completed Phase 4

~10830

Mitoxantrone Hydrochloride

2016

Completed Phase 3

~650

Etoposide

2010

Completed Phase 3

~2960

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Myeloid Leukemia include chemotherapy, targeted therapy, and sometimes immunotherapy. Chemotherapy works by killing rapidly dividing cancer cells, which helps to reduce the number of leukemic cells in the body. Targeted therapies, such as tyrosine kinase inhibitors, specifically inhibit molecules involved in the growth and survival of cancer cells, thereby stopping them from dividing and spreading. Immunotherapy boosts the body's immune system to recognize and destroy cancer cells. These treatments are essential for Myeloid Leukemia patients as they address the aggressive nature of the disease by directly targeting the mechanisms that allow leukemic cells to proliferate and spread.

Molecular targeting in acute myeloid leukemia.Targeting phosphatidylinositol 3-kinase signaling in acute myelogenous leukemia.Remission induction, consolidation and novel agents in development for adults with acute myeloid leukaemia.