A Phase I Study of Autologous Activated Natural Killer (NK) Cells +/- rhIL15 in Children and Young Adults With Refractory Solid Tumors
- Despite progress, some children and young adults with solid tumors still experience
- Activated NK cells potently kill autologous pediatric solid tumors, and clinical grade
procedures are available to generate large numbers of activated NK cells for adoptive
- Primary objectives are: 1) to assess the feasibility of harvesting and expanding
activated NK cells to meet escalating dose goals in Cohort A, 2) to assess the toxicity
of infusing escalating doses of activated NK cells following lymphodepleting
chemotherapy without rhIL15 (cohort A), and 3) to assess the toxicity of infusing NK
activated cells with escalating doses of rhIL15 (cohort B) in pediatric patients with
refractory malignant solid tumors.
- Secondary objectives are: 1) to identify biologically active doses of activated
autologous NK cells plus or minus rhIL15 by monitoring changes in NK cell number,
phenotype and function, 2) to assess pharmacokinetics and immunogenicity of rhIL15 in a
pediatric population, and 3) assess antitumor effects and changes in FDG-PET following
administration of activated NK cells to lymphopenic hosts plus or minus rhIL15.
- Patients 2-25 years with refractory pediatric malignant solid tumors.
- Adequate performance status and organ function, recovered from toxic effects of prior
therapy, no requirement for systemic corticosteroids and no history of allogeneic stem
- All patients receive pre-NK lymphodepleting chemotherapy with cyclophosphamide.
- Cohort A receives escalating doses of activated autologous NK cells to identify
feasibility of generating cells and tolerability, and potentially identify an MTD.
- A1: 1x10(6) NK cells/kg
- A2: 1 x 10(7) NK cells/kg
- A3: 1 x 10(8) NK cells/kg
- If feasibility and acceptable toxicity is demonstrated for all doses in Cohort A,
patients enrolled on cohort B will receive activated autologous NK cells plus
escalating doses of rhIL15 using the following schema:
- B1: 1 x 10(7) NK cells/kg + rhIL15 0.25 mcg/kg/d IV x 12
- B2: 1 x 10(8) NK cells/kg + rhIL15 0.25 mcg/kg/d IV x 12
- B3: 1 x 10(8) NK cells/kg + rhIL15 0.5 mcg/kg/d IV x 12
- B4: 1 x 10(8) NK cells/kg + rhIL15 0.75 mcg/kg/d IV x 12
- Three patients will be enrolled at each dose level, with the dose level expanded to 6
if doselimiting toxicity occurs. An expanded group of 12 patients will be treated at
the highest tolerable dose level. DLT toxicity monitoring will continue for 21 days
after the NK infusion, or 14 days after the last rhIL15 dose in Cohort B (whichever is
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Assess feasibility of harvesting + expanding activated NK cells in escalating doses in Cohort A;and assess toxicity of autologous activated and expanded NK cells following lymphodepleting chemotherapy + or - rhIL15 in pediatric patients w/ solid...
Melinda S Merchant, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|