A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations

Summary

This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.

Timeline

Start

2020-07-21

Primary completion

2029-06-30

Completion

2029-06-30

Publications

• Leger KJ, Absalon MJ, Demissei BG, Smith AM, Gerbing RB, Alonzo TA, Narayan HK, Hirsch BA, Pollard JA, Razzouk BI, Getz KD, Aplenc R, Kolb EA, Ky B, Cooper TM. Cardiotoxicity of CPX-351 in children and adolescents with relapsed AML: a Children's Oncology Group report. Front Cardiovasc Med. 2024 Jun 14;11:1347547. doi: 10.3389/fcvm.2024.1347547. eCollection 2024.
• Leger KJ, Robison N, Narayan HK, Smith AM, Tsega T, Chung J, Daniels A, Chen Z, Englefield V, Demissei BG, Lefebvre B, Morrow G, Dizon I, Gerbing RB, Pabari R, Getz KD, Aplenc R, Pollard JA, Chow EJ, Tang WHW, Border WL, Sachdeva R, Alonzo TA, Kolb EA, Cooper TM, Ky B. Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy. Front Cardiovasc Med. 2023 Dec 1;10:1286241. doi: 10.3389/fcvm.2023.1286241. eCollection 2023.
• Andolina JR, Fries C, Boulware R, Vargas A, Fraint E, Barth M, Ambrusko S, Comito M, Monteleone P. Successful Bone Marrow Transplantation With Intensive Post-transplant Intrathecal Chemotherapy for CNS Relapsed AML in 2 Infants. J Pediatr Hematol Oncol. 2022 Jan 1;44(1):e264-e267. doi: 10.1097/MPH.0000000000002151.

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Indications