This phase I trial studies how well a modified chemotherapy regimen with gemtuzumab ozogamicin works for the treatment of newly diagnosed acute myeloid leukemia in pediatric patients. The current standard of care to treat most pediatric patients with acute myeloid leukemia is 5 cycles of chemotherapy. Adjusting treatment with a 4-cycle treatment regimen may provide the same treatment results and decrease the amount of side effects experienced during treatment. Gemtuzumab ozogamicin is a monoclonal antibody, gemtuzumab, linked to a toxic agent called calicheamicin. Gemtuzumab attaches to CD33 positive cancer cells in a targeted way and delivers calicheamicin to kill them. Giving gemtuzumab ozogamicin with the 4-cycle treatment regimen may also reduce the chances of acute myeloid leukemia coming back after initial treatment.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04326439.
PRIMARY OBJECTIVE:
I. To estimate the event-free survival (EFS) for newly diagnosed patients with pediatric acute myeloid leukemia using a risk stratified approach, including a modified chemotherapy regimen alone for subjects with low-risk features and allogeneic bone marrow transplantation for those with high risk features.
SECONDARY OBJECTIVES:
I. To estimate the overall survival (OS) for newly diagnosed patients with pediatric acute myeloid leukemia.
II. To estimate frequency of minimal residual disease (MRD) negative status after one cycle of induction chemotherapy for acute myeloid leukemia (AML) patients who received gemtuzumab ozogamicin (GO) and those that did not receive GO.
III. To estimate the disease-free survival (DFS) for patients who are minimal residual disease (MRD) negative after induction 1, but lack high risk or lowest risk molecular and cytogenetic features as currently classified.
IV. To estimate the incidence of early and late cardiotoxicity in patients with de novo AML that receive the four-cycle Aflac-AML regimen with the inclusion of dexrazoxane.
V. To estimate the frequency of infection and/or febrile neutropenia by chemotherapy regimen.
EXPLORATORY OBJECTIVE:
I. To describe the prevalence of molecular abnormalities in de-novo AML samples using comprehensive genomic testing.
OUTLINE:
INDUCTION I: Patients receive cytarabine intrathecally (IT) at time of diagnostic lumbar puncture or on day 1, cytarabine intravenously (IV) over 1-2 minutes on days 1-10, daunorubicin hydrochloride IV over 15 minutes on days 1, 3, and 5, etoposide phosphate IV over 60-120 minutes on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on days 6-10. Patients with FLT3-ITD also receive sorafenib tosylate orally (PO) daily on days 11-28. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
INDUCTION II: Patients receive cytarabine IT on day 1, high dose cytarabine IV over 1-3 hours on days 1-4, mitoxantrone IV over 15-30 minutes on days 3-6. Patients with FLT3-ITD also receive sorafenib tosylate PO daily on days 7-34. Treatment continues for 28 or 34 days in the absence of disease progression or unacceptable toxicity.
INTENSIFICATION I: Patients receive cytarabine IT on day 1, high dose cytarabine IV over 1-3 hours on days 1-5, and etoposide phosphate IV over 60-120 minutes on days 1-5. Patients with FLT3-ITD also receive sorafenib tosylate PO daily on days 6-33. Treatment continues for 28 or 33 days in the absence of disease progression or unacceptable toxicity.
INTENSIFICATION II: Patients receive high dose cytarabine IV over 1-3 hours on days 1, 2, 8, and 9 and asparaginase Erwinia chrysanthemi intramuscularly (IM) or IV over 1 hour on days 2 and 9. Patients with FLT3-ITD also receive sorafenib tosylate PO daily on days 11-28. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up annually for 10 years.
Lead OrganizationChildren's Healthcare of Atlanta - Arthur M Blank Hospital
Principal InvestigatorHimalee Shreekant Sabnis
