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

Completed · Phase 1

Conditions studied: Solid Tumors, Brain Tumors, Sarcoma, Pediatric Cancers, Neuroblastoma

In brief

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).

Key facts

Study ID: NCT01875601
Run by: National Cancer Institute (NCI)
People needed: 16
Starts: 2013-06-11
Expected to finish: 2015-09-08
Last updated by the study team: 2026-08-07

Who can join

Age: 2 and older, up to 29. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Untreated CNS metastatic disease as defined by:
Solid Tumors: History of untreated metastatic CNS tumor involvement. Extradural masses which have not invaded the brain parenchyma or parameningeal tumors without evidence for leptomeningeal spread will not render the patient ineligible. Patients with previous CNS tumor involvement are eligible IF the CNS tumor(s) has been treated and has been stable or resolving for at least 4 weeks; and if the patient does not currently require steroids.
Prior history allogeneic stem cell transplantation.
Breast feeding or pregnant females (due to risk to fetus or newborn).
HIV or HTLV-I/II (due to unacceptable risk associated with severe immune suppression and risk associated with cell products).
Hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody positive with elevated liver transaminases. All patients with chronic active hepatitis (including those on antiviral therapy) are ineligible.
Patients who require systemic corticosteroid or other systemic immunosuppressive therapy. Immunosuppressive therapy must be stopped at least 28 days prior to enrollment. Topical agents and/or inhaled corticosteroids are permitted.
High risk of inability to comply with therapy in the estimation of the PI.
Clinically significant systemic illness (e.g. serious active infections or significant vital other organ dysfunction), that in the judgment of the PI would likely compromise the patient s ability to tolerate protocol therapy or significantly increase the risk of complications.
Prior history of pericarditis or pericardial effusion.
INCLUSION OF WOMEN AND MINORITIES:
Both men and women of all races and ethnic groups are eligible for this trial.

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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