NCT03209869

Treatment of Relapsed or Refractory Neuroblastoma and Osteosarcoma With Expanded Haploidentical NK Cells and Hu14.18-IL2

Treatment of Relapsed or Refractory Neuroblastoma and Osteosarcoma With Ex-Vivo Expanded and Activated Haploidentical NK Cells and Hu14.18-IL2

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 7 Months – 25 Years
• Healthy volunteers: Not accepted

Summary

Subjects with relapsed or refractory neuroblastoma and osteosarcoma will receive ex-vivo expanded and activated natural killer (NK) cells from a haploidentical donor in conjunction with the immunocytokine, hu14.18-IL2.

Detailed description

Natural Killer cells, a type of white blood cell, circulate around the body and kill abnormal cells (cells that are malignant, damaged or infected with virus). Sometimes cancer cells adapt to the body's own NK cells and are able to avoid being killed by them. This clinical trial uses two strategies to overcome the cancer cells' ability to avoid NK cell-mediated death. The first strategy involves giving NK cells from another individual to the patient (in other words, donor- or haploidentical-NK cells). This is done because NK cells from an individual who is haploidentical (half-matched genetic make-up) are still able to effectively kill the cancer cells. Unfortunately, only a limited number of NK cells can be obtained from a donor. So, to increase the number of cancer-killing NK cells that will be given to the patient, the donor NK cells will first be grown in a sterile laboratory environment and allowed to multiply many-fold before they are infused into the patient. This growing process also activates the donor NK cells, which increases their ability to kill cancer cells. The second strategy to overcome the cancer cells' ability to avoid NK cell-mediated death is to administer the immunocytokine, hu14.18-IL2, every day for seven days after infusion of the donor NK cells. The antibody portion (hu14.18) of the immunocytokine molecule "flags" the neuroblastoma cells for destruction by NK cells and the cytokine portion (IL2) further activates the NK cells (as well as other anti-tumor immune effector cells). Since the donor NK cells are from a haploidentical individual, they are different enough to be recognized as foreign cells and will be killed immediately ("rejected") by the patients own immune system unless the immune system is restrained. So, to allow the donor NK cells time to kill neuroblastoma cells before they are "rejected", a chemotherapy regimen is first given to the patient to temporarily restrain the patient's own immune system. This also allows "room" for the donor NK cells to live, multiply and function. Four courses of treatment are planned for each subject. Each course of treatment will be approximately one month long and involves a week of chemotherapy followed by infusion of donor NK cells. Beginning the day after the donor NK cell infusion, hu14.18-IL2 is infused over four hours for seven consecutive days.

Conditions

• Neuroblastoma
• Relapsed Neuroblastoma
• Recurrent Neuroblastoma
• Osteosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	Ex vivo Expanded and Activated Haploidentical Donor NK Cells	Haploidentical donor NK cells that are expanded and activated under current GMP conditions using K562-mbIL15-41BBL.
BIOLOGICAL	Hu14.18-IL2	The immunocytokine, hu14.18-IL2, is a fusion protein comprised of one molecule of the anti-GD2 humanized monoclonal antibody, hu14.18, fused to two molecules of the cytokine, interleukin-2.

Timeline

• Start date: 2018-03-12
• Primary completion: 2022-09-07
• Completion: 2022-09-07
• First posted: 2017-07-06
• Last updated: 2022-09-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study