This phase I/II trial studies the side effects and best dose of donor natural kill cells and to see how well they work in treating patients with acute myeloid leukemia that does not respond to treatment (refractory) or has come back after a period of improvement (relapsed). Giving natural killer cells after high dose chemotherapy may boost the patient's immune system by helping it see the remaining cancer cells as not belonging in the patient's body and causing it to destroy them (called graft-versus-tumor effect).
PRIMARY OBJECTIVES: I. Determine the safety, feasibility, and maximum tolerated dose of membrane-bound interleukin 21 (mbIL21)-expanded haploidentical natural killer (NK) cells after induction chemotherapy with fludarabine (fludarabine phosphate), cytarabine, and filgrastim-sndz, Zarxio (filgrastim-sndz) (G-CSF) (FLAG). SECONDARY OBJECTIVES: I. Determine the persistence of adoptively-transferred expanded NK cells. II. Determine the immunophenotype and function of expanded NK cells. III. Determine the overall response of acute myeloid leukemia (AML) to this regimen. IV. Correlate NK cell persistence, phenotype, and function with overall response. V. Estimate the rate at which patients receiving this regimen are able to go to transplant. OUTLINE: This is a phase I, dose-escalation study of membrane-bound interleukin-21-expanded haploidentical natural killer cells followed by a phase II study. Patients receive filgrastim-sndz subcutaneously (SC) once daily (QD) beginning on day -7 and continuing until absolute neutrophil counts (ANC) are equal or over 1000. Patients also receive fludarabine phosphate intravenously (IV) over 30 minutes and approximately 4 hours later followed by cytarabine IV over 1 hour on days -6 to -2 (days -6 to -3 for patients over age 60). Beginning 2-7 days after the last dose of fludarabine phosphate and cytarabine, patients receive membrane-bound interleukin-21-expanded haploidentical natural killer cells IV over 30 minutes thrice weekly for 3 doses over 4 days (Monday-Thursday only). After completion of study treatment, patients are followed up for 56 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given IV
Given SC
Given SC
Given IV
Correlative studies
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose of natural killer (NK) cells, defined as the highest dose level at which no more than 2 patients in a 6-patient cohort experience a dose limiting toxicity during treatment
Time frame: Day 28
Complete remission rate (CR)
Estimated with Kaplan-Meier estimator and tabulated with 95% confidence intervals. Cox proportional hazards regression will be used to model CR as a function of NK cell dose.
Time frame: Day 56 following infusion of the NK cells
NK-cell numerical expansion in vivo defined as an absolute circulating donor-derived NK cell count that increases above the post-infusion level
Proportion of patients with successful in vivo NK-cell expansion estimated with a 95% confidence interval.
Time frame: Up to day 56
Time to transplantation (TTT)
Estimated with Kaplan-Meier estimator and tabulated with 95% confidence intervals. Cox proportional hazards regression will be used to model TTT as a function of NK cell dose.
Time frame: Up to day 56
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