Chemotherapy for Pediatric Acute Myeloid Leukemia

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: CNS pathology, Active infections, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and understand the side effects of three chemotherapy drugs for children with acute myeloid leukemia (AML) that has recurred or is unresponsive to treatment. The drugs being tested include liposomal cytarabine and daunorubicin, which inhibit cancer cell growth, and gemtuzumab ozogamicin, which targets and kills specific cancer cells. The trial specifically seeks pediatric patients with CD33 positive AML or AML developed after myelodysplastic syndrome (MDS). Participants should exhibit visible signs of leukemia and not have other uncontrolled health issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive potentially groundbreaking therapy.

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 chemotherapy, radiotherapy, or investigational therapy should not be taken within 2 weeks before starting the study drugs, except for certain medications like cytarabine or hydroxyurea, which do not require a washout period (time without taking certain medications).

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

Research has shown that gemtuzumab ozogamicin, one of the treatments in this trial, is already approved by the FDA for treating certain types of leukemia. This approval indicates its safety for patients with similar conditions. Studies involving children and teenagers have demonstrated that gemtuzumab ozogamicin improves survival by reducing the likelihood of cancer recurrence.

Regarding the combination of CPX-351 and gemtuzumab ozogamicin, studies have reported positive results in patients who underwent multiple prior treatments. However, these studies also noted varying responses among patients.

As this is an early-phase trial, researchers are determining the safest dose and monitoring for side effects. This phase primarily ensures the treatment's safety before testing it on larger patient groups. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pediatric acute myeloid leukemia because they combine CPX-351 and Gemtuzumab Ozogamicin (GO) to potentially offer a more effective option. Unlike traditional chemotherapy treatments like standard Cytarabine and Daunorubicin, CPX-351 is a liposomal formulation that delivers drugs in a precise ratio, improving drug delivery to cancer cells. Gemtuzumab Ozogamicin, an antibody-drug conjugate, specifically targets leukemia cells, potentially reducing harm to healthy cells. Together, these treatments aim to enhance effectiveness and reduce side effects, offering hope for better outcomes in young patients.

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

Research has shown that CPX-351 and gemtuzumab ozogamicin, studied in this trial, may help treat acute myeloid leukemia (AML). Studies have found that gemtuzumab ozogamicin effectively targets and destroys leukemia cells with a common marker called CD33. CPX-351, a mix of chemotherapy drugs, has also improved outcomes for AML patients. Additionally, researchers have tested the safety and potential effectiveness of using these drugs together. These treatments work by directly attacking cancer cells and preventing their growth and spread. ^{3 4 6 7 8}

Who Is on the Research Team?

Branko Cuglievan

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for pediatric patients up to 21 years old with relapsed or refractory acute myeloid leukemia (AML) that's CD33 positive. They should have a certain level of organ function, not be pregnant or breastfeeding, and agree to use effective contraception. Excluded are those with heart issues, high doses of prior chemotherapy, active infections, other cancers in the last few years except certain skin cancers or localized cancers.

Inclusion Criteria

Total serum bilirubin =< 2 x upper limit of normal (ULN); =< 3 x ULN for patients with known Gilbert's syndrome

I can do most activities but need help with some, regardless of my age.

I have acute myeloid leukemia with at least 5% cancer cells in my blood or bone marrow.

Exclusion Criteria

I am currently receiving treatment for GvHD.

My heart's pumping ability is below normal.

I have active brain or spinal cord disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction 1

Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and GO IV over 2 hours on day 1

4 weeks

Induction 2

Patients who do not attain a defined clinical response after Induction 1 receive CPX-351 IV on days 1 and 3 and GO IV over 2 hours on day 1

4 weeks

Consolidation

Beginning 4 weeks after last induction, patients receive CPX-351 IV over 90 minutes on days 1 and 3 and GO IV over 2 hours on day 1

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Gemtuzumab Ozogamicin

Trial Overview The trial tests liposomal cytarabine and daunorubicin alongside gemtuzumab ozogamicin for AML in children who've had treatment fail before. It aims to find the best dose and monitor side effects by seeing how these drugs stop cancer cells from growing.

How Is the Trial Designed?

Group I: Treatment (CPX-351, GO) Experimental Treatment 2 Interventions

INDUCTION 1 (28 days): Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 and GO IV over 2 hours on day 1 in the absence of disease progression or unacceptable toxicity. INDUCTION 2: Patients who do not attain a defined clinical response after cycle Induction 1 receive CPX-351 IV on days 1 and 3 and GO IV over 2 hours on day 1 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Beginning 4 weeks after last induction, patients receive CPX-351 IV over 90 minutes on days 1 and 3 and GO IV over 2 hours on day 1 in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/967/531036/A-Phase-3-Randomized-Trial-for-Patients-with-De

A Phase 3 Randomized Trial for Patients with De Novo AML ... A Phase 3 randomized trial for patients with de novo AML comparing standard therapy including Gemtuzumab Ozogamicin (GO) to CPX-351 with GO.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124037145

A Phase 3 Randomized Trial for Patients with De Novo ... The Children's Oncology Group (COG) Phase III clinical trial AAML1831 tested the hypothesis that CPX-351 given during Inductions 1 and 2 would improve ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05558124

Study Details | NCT05558124 | CPX-351 in Combination ... The purpose of the study is to determine the safety of combining the drugs gemtuzumab ozogamicin (GO) with CPX-351 in order to treat the disease, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7789799/

Paediatric Strategy Forum for medicinal product development ... Although the efficacy of gemtuzumab ozogamicin has been demonstrated in subgroups of AML, particularly those with high CD33 expression, CC genotype and/or FLT3 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05558124?term=AREA%5BInterventionSearch%5D(%22Gemtuzumab%22)&rank=9

CPX-351 in Combination With Gemtuzumab Ozogamicin ... The purpose of the study is to determine the safety of combining the drugs gemtuzumab ozogamicin (GO) with CPX-351 in order to treat the disease, ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2903/533109/Combination-of-CPX-351-and-Gemtuzumab-Ozogamicin

Combination of CPX-351 and Gemtuzumab Ozogamicin (GO ... GO is a humanized IgG4 antibody-drug conjugate against CD33 and is approved by FDA for the treatment of newly diagnosed or R/R pediatric and ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124056556

Combination of CPX-351 and Gemtuzumab Ozogamicin ... The combination of CPX-GO in pts with R/R AML and HR-MDS led to modest responses. OS was meaningful in responders, considering multiple prior lines of therapy.

8. siope.eu siope.eu/media/documents/acute-myeloid-leukemia.pdf

Acute Myeloid Leukemia (AML) in Children and Adolescents ... Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from ...