Clinical Research Directory

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

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).

Follow-Up Evaluation for Gene-Therapy-Related Delayed Adverse Events After Participation in Pediatric Oncology Branch Clinical Trials

Background: \- Gene therapy involves changing the genes inside the body s cells to stop disease. It is very closely regulated. People who have had this therapy may have problems months or even years later. Researchers do not know the long-term side effects, so they want to study people who have had the therapy. They want the study to continue over the next 15 years. Objective: \- To study over time the negative side effects from genetically engineered cellular therapy. This will be studied in people who have been in Pediatric Oncology Branch (POB) gene therapy trials. Eligibility: \- People who are currently or were previously in a research study with gene therapy in the National Cancer Institute POB. Design: * Participants blood will be tested right before they get the genetically changed cells. They will get the cells as part of another study. * For the next year, they will come back to the clinic or see their doctor at home at least every 3 months. They will answer questions about their health and blood will be drawn. * For the next 5 years, they will go to the clinic or see their own doctor once a year. They will have physical exam and blood will be drawn. * For 10 years after that, they will be asked every year for health information. * Participants will keep their contact information up to date with researchers. They may be phoned for more health information. * If the participant was under 18 years old when given the gene therapy and turns 18 during this follow-up, they will be asked to sign a new consent form when they turn 18.

Safety and Efficacy of CMD03 CAR T Cell in Children With Relapse or Refractory Solid Tumors

A Phase 1 clinical trial to evaluate the safety and early efficacy of CAR T-cells with IL-7Ra signal targeting B7H3 in children with solid tumors patients after complete standard treatments.