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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-12

Study Completion Date

2022-09-07

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

hu14.18-Interleukin-2 Fusion Protein in Treating Young Patients With Recurrent or Refractory Neuroblastoma

NCT00082758

Neuroblastoma

COMPLETED PHASE2

Combination Chemotherapy, Monoclonal Antibody, and Natural Killer Cells in Treating Young Patients With Recurrent or Refractory Neuroblastoma

NCT01576692

Neuroblastoma

COMPLETED PHASE1

Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors

NCT00003750

Melanoma (Skin) Neuroblastoma Sarcoma +1 more

COMPLETED PHASE1

Allogeneic Expanded Gamma Delta T Cells With GD2 Chemoimmunotherapy in Relapsed /Refractory Neuroblastoma or Refractory/ Relapsed Osteosarcoma

NCT05400603

Neuroblastoma Refractory Neuroblastoma Relapsed Neuroblastoma +2 more

RECRUITING PHASE1

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Neuroblastoma

NCT00017368

Neuroblastoma

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Neuroblastoma Relapsed Neuroblastoma Recurrent Neuroblastoma Osteosarcoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Single arm

All subjects will receive Ex vivo Expanded and Activated Haploidentical Donor NK Cells + hu14.18-IL2

Group Type EXPERIMENTAL

Ex vivo Expanded and Activated Haploidentical Donor NK Cells

Intervention Type BIOLOGICAL

Haploidentical donor NK cells that are expanded and activated under current GMP conditions using K562-mbIL15-41BBL.

Hu14.18-IL2

Intervention Type BIOLOGICAL

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

EANK cells Immunocytokine

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)

Minimum Eligible Age

7 Months

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No