NK White Blood Cells and Interleukin in Children and Young Adults With Advanced Solid Tumors

Sarcoma Clinical Trial

Official title: A Phase I Study of Autologous Activated Natural Killer (NK) Cells +/- rhIL15 in Children and Young Adults With Refractory Solid Tumors

Status Completed

Clinical Trial Summary

BACKGROUND:

• Despite progress, some children and young adults with solid tumors still experience poor survival.

• 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 cell therapy.

OBJECTIVES:

• 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. 4) to evaluate saftey and efficacy of subsequent cycles of autologous NK cell infusions in patients in cohort A who received benefit from the first NK cell infusion.

ELIGIBILITY:

• Patients in Cohort A: 2-29 years with with refractory pediatric malignant solid tumors, Patients in Cohort B: 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 cell transplantation.

DESIGN:

• 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 10

• B2: 1 x 10(7) NK cells/kg + rhIL15 0.5 mcg/kg/d IV x 10

• B3: 1 x 10(7) NK cells/kg + rhIL15 1 mcg/kg/d IV x 10

• B4: 1 x 10(7) NK cells/kg + rhIL15 2 mcg/kg/d IV x 10

• Three patients will be enrolled at each dose level, with the dose level expanded to 6 if dose-limiting 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 later).

Clinical Trial Description

BACKGROUND:

• Despite progress, some children and young adults with solid tumors still experience poor survival.

• 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 cell therapy.

OBJECTIVES:

• 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. 4) to evaluate saftey and efficacy of subsequent cycles of autologous NK cell infusions in patients in cohort A who received benefit from the first NK cell infusion.

ELIGIBILITY:

• Patients in Cohort A: 2-29 years with with refractory pediatric malignant solid tumors, Patients in Cohort B: 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 cell transplantation.

DESIGN:

• 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 10

• B2: 1 x 10(7) NK cells/kg + rhIL15 0.5 mcg/kg/d IV x 10

• B3: 1 x 10(7) NK cells/kg + rhIL15 1 mcg/kg/d IV x 10

• B4: 1 x 10(7) NK cells/kg + rhIL15 2 mcg/kg/d IV x 10

• Three patients will be enrolled at each dose level, with the dose level expanded to 6 if dose-limiting 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 later). ;

Related Conditions & MeSH terms

• Brain Tumors
• Neoplasms
• Neuroblastoma
• Pediatric Cancers
• Sarcoma
• Solid Tumors

• NCT number: NCT01875601
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: June 11, 2013
• Completion date: September 8, 2015