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

University of Wisconsin (UW)

Status and phase

Withdrawn

Phase 1

Conditions

Osteosarcoma

Relapsed Neuroblastoma

Neuroblastoma

Recurrent Neuroblastoma

Treatments

Biological: Hu14.18-IL2

Biological: Ex vivo Expanded and Activated Haploidentical Donor NK Cells

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT03209869

2016-1195 (Other Identifier)

NCI-2017-01267 (Registry Identifier)

A536755 (Other Identifier)

P30CA014520 (U.S. NIH Grant/Contract)

SMPH/PEDIATRICS/PEDIATRICS (Other Identifier)

UW16009

Protocol V12 01/30/2021 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

7 months to 25 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Relapsed or refractory neuroblastoma
Relapsed or refractory Osteosarcoma
Karnofsky/Lansky performance score > 50
Life expectancy ≥ 4 months
Creatinine clearance or radioisotope GFR ≥ 60 ml/min/1.73m2 OR serum creatinine within normal limits based on age and gender
ANC ≥ 750/µL
Platelet count ≥ 50,000/µL
Hemoglobin ≥ 8 g/dL
Total bilirubin ≤ 1.5 x upper limit of normal for age
ALT (SCPT) ≤ 5 x upper limit of normal for age
Shortening fraction of ≥ 27% by echocardiogram OR Ejection fraction of ≥55% by MUGA
No evidence of dyspnea at rest
Pulse oximetry > 94% on room air
If PFTs performed, FEV1/FVC must be > 60%
All Osteosarcoma patients must have PFTs performed
CNS toxicity ≤ Grade 2
Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsant therapy
> 100 days after autologous stem cell infusion following myeloablative therapy
≥ 2 weeks since chemotherapy
≥ 7 days since anti-neoplastic, non-myelosuppressive biologic agent (or extended for agents known to have adverse events beyond the 7- day period)
≥ 2 weeks for local palliative XRT
≥ 6 months if prior craniospinal axis XRT (> 50%)
≥ 6 months if > 50% radiation of pelvis
≥ 6 weeks after therapeutic 131I-MIBG
≥ 6 weeks since thoracotomy
Informed consent obtained (patient or legal representative)
Women of reproductive potential must have negative pregnancy test and be willing to use effective birth control method
Suitable haploidentical donor must be available

Exclusion criteria

Prior history of ventilator support related to lung injury, except for immediately following thoracotomy
Symptomatic pleural effusions or ascites
<6 weeks from thoracotomy and <2 weeks from other major surgery
History of anaphylaxis while receiving prior anti-GD2 therapy
Pregnant
HIV infection
Heart failure or uncontrolled cardiac rhythm disturbance
Active infection
Prior organ allograft
Prior allogeneic bone marrow or peripheral blood stem cell transplant
Significant serious intercurrent illnesses expected to interfere with the antitumor effect of treatment or to significantly increase the severity of toxicities experienced from treatment
Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study.
Enrollment in any other treatment study from screening up to 28 days after the last treatment on this study (unless PI judges such enrollment would not interfere with endpoints of this study)