This phase II trial studies how well CPX-351 or the CLAG-M regimen (consisting of the drugs cladribine, cytarabine, G-CSF, and mitoxantrone) works in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms. Drugs used in chemotherapy, such as CPX-351, cladribine, cytarabine, G-CSF, and mitoxantrone, 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. Giving CPX-351 or the CLAG-M regimen at doses typically used for medically-fit patients with acute myeloid leukemia may work better than reduced doses of CPX-351 in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04195945.
PRIMARY OBJECTIVE:
I. To evaluate whether liposome-encapsulated daunorubicin-cytarabine (CPX-351) or cladribine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and mitoxantrone (CLAG-M), at doses typically used for medically-fit adults with acute myeloid leukemia (AML), improve 3 month overall survival in medically-unfit adults with AML compared to attenuated dose CPX-351 as used in our previous institutional trial (32 units/m^2 per dose).
SECONDARY OBJECTIVES:
I. To compare complete remission (CR) rates, minimal residual disease negative (MRDneg) CR rates, response duration, and relapse free survival (RFS) between the study arms.
II. To describe the toxicity profile and infectious complications of each study treatment as well as 30- and 60-day mortality rate.
III. To evaluate the impact of treatment on quality of life (QOL) for patients undergoing the two therapies.
IV. To describe the impact of each study treatment on medical resource utilization.
OUTLINE: Patients are randomized to 1 of 2 arms in a 1:1 fashion. ARM I = CPX-351; ARM II = CLAG-M.
ARM I (INDUCTION): Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of CPX-351 intravenously IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.
ARM I (POST-REMISSION): Patients who achieve a CR or CR with incomplete hematologic recovery (CRi) receive a reduced dose of CPX-351 IV over 90 minutes on days 1, 3, and 5 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.
ARM II (INDUCTION): Patients receive cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF subcutaneously (SC) on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity.
ARM II (POST-REMISSION): Patients who achieve a CR/CRi receive an intermediate dose of cytarabine IV over 2 hours on days 1-6 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 5 years.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorRoland Bruno Walter
