NCT01875601

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

Completed Phase 1 Last updated 14 April 2026

What this trial tests

Phase 1 trial testing Recombinant human interleukin-15 (rhIL-15) in Solid Tumors in 16 participants. Completed in 8 September 2015.

Timeline

11 June 2013

Primary endpoint
8 September 2015

8 September 2015

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	16
Start date	11 June 2013
Primary completion	8 September 2015
Estimated completion	8 September 2015
Sites	1 location across United States

Drugs / interventions tested

• Recombinant human interleukin-15 (rhIL-15) — full drug profile →
• NK Cell Infusion — full drug profile →

Conditions studied

• Solid Tumors — all drugs for Solid Tumors →
• Brain Tumors — all drugs for Brain Tumors →
• Sarcoma — all drugs for Sarcoma →
• Pediatric Cancers — all drugs for Pediatric Cancers →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 2 to 29, any sex, with Solid Tumors or Brain Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own 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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cytokines in clinical cancer immunotherapy.
   Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, et al · · 2019 · cited 834× · PMID 30413827 · DOI 10.1038/s41416-018-0328-y
2. NK cell-based cancer immunotherapy: from basic biology to clinical development.
   Liu S, Galat V, Galat Y, Lee YKA, et al · · 2021 · cited 504× · PMID 33407739 · DOI 10.1186/s13045-020-01014-w
3. Continuous treatment with IL-15 exhausts human NK cells via a metabolic defect.
   Felices M, Lenvik AJ, McElmurry R, Chu S, et al · · 2018 · cited 210× · PMID 29415897 · DOI 10.1172/jci.insight.96219
4. The Application of Natural Killer Cell Immunotherapy for the Treatment of Cancer.
   Rezvani K, Rouce RH. · · 2015 · cited 202× · PMID 26635792 · DOI 10.3389/fimmu.2015.00578
5. Molecular pathways: interleukin-15 signaling in health and in cancer.
   Mishra A, Sullivan L, Caligiuri MA. · · 2014 · cited 182× · PMID 24737791 · DOI 10.1158/1078-0432.ccr-12-3603
6. The potential and promise of IL-15 in immuno-oncogenic therapies.
   Robinson TO, Schluns KS. · · 2017 · cited 155× · PMID 28823521 · DOI 10.1016/j.imlet.2017.08.010
7. NK cell infiltration is associated with improved overall survival in solid cancers: A systematic review and meta-analysis.
   Nersesian S, Schwartz SL, Grantham SR, MacLean LK, et al · · 2021 · cited 153× · PMID 33186888 · DOI 10.1016/j.tranon.2020.100930
8. Natural killer cells: a promising immunotherapy for cancer.
   Chu J, Gao F, Yan M, Zhao S, et al · · 2022 · cited 140× · PMID 35606854 · DOI 10.1186/s12967-022-03437-0