NK White Blood Cells and Interleukin in Children and Young Adults With Advanced Solid Tumors
- Natural Killer (NK) cells are white blood cells that are important in helping the body fight viruses and tumors. Studies show that NK cells are important to attack leukemia cells after bone marrow transplants. They have also been shown to kill solid tumor cells. Researchers plan to combine NK cells with an immune-boosting drug called interleukin 15 (IL-15). They want to see if NK cells and IL-15 can be used to treat children and young adults who have solid tumors that have not responded to other treatments.
- To study the safety and effectiveness of NK cells and IL-15 in children and young adults with advanced solid tumors.
- Children and young adults between 2 and 25 years of age who have advanced solid tumors that have not responded to standard treatments.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will be used to monitor the cancer before treatment.
- Participants will have apheresis to provide NK white blood cells for the study. The NK cells will be collected from the blood.
- Participants will have inpatient chemotherapy to prepare for the NK cell and IL-15 treatment.
- After the chemotherapy, participants will receive the NK cells over several days. They will also receive IL-15 to help the immune system respond to the cells.
- After recovering in the hospital, participants will be monitored closely at home. They will have frequent blood tests and imaging studies. They may also have another apheresis to collect NK white blood cells again for study.
Biological: Recombinant human interleukin-15 (rhIL-15)
Biological: NK Cell Infusion
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Autologous Activated Natural Killer (NK) Cells +/- rhIL15 in Children and Young Adults With Refractory Solid Tumors|
- MTD & amp; Toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Feasibility [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- pharmacokinetics & amp; immunogenicity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- biologically active doses [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- antitumor activity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- safety & amp; efficacy of Cohort A [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||November 2022|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
two cohorts, one with only NK cell infusion (dose escalation), and one with NK Cell Infusion + rhIL15 (dose escalation)
Biological: Recombinant human interleukin-15 (rhIL-15)
Administered on Day 0 in combination with NK Cell Infusion (dose escalation: rhIL15 0.25 mcg/kg/d IV x 12; rhIL15 0.25 mcg/kg/d IV x 12; rhIL15 0.5 mcg/kg/d; rhIL15 0.75 mcg/kg/d IV x 12)Biological: NK Cell Infusion
Infuse expanded NK cells at Day 0 (dose escalation: 1x106 NK cells/kg; 1 x 107 NK cells/kg; 1 x 108 NK cells/kg) after 2 days Cyclophosphamide + Mesna (1800mg/m2), daily filgrastim/pegfilgrastim (5mcg/kg)
- 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.
- 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.
- 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.
- 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 0.25 mcg/kg/d IV x 10
- B3: 1 x 10(7) NK cells/kg + rhIL15 0.5 mcg/kg/d IV x 10
- B4: 1 x 10(7) NK cells/kg + rhIL15 0.75 mcg/kg/d IV x 10
- 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 later).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01875601
|Contact: Melinda S Merchant, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Melinda S Merchant, M.D.||National Cancer Institute (NCI)|