Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Sarcoma, Ewing

Rhabdomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Myosarcoma

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Analgesics

Central Nervous System Depressants

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Morphine

Immunosuppressive Agents

Intravenous infusion of expanded, activated NK Cells Donor cell will be expanded and activated in the cGMP compliant TECT lab for 10 to 12 days prior to infusion into the patient.

1. Chemotherapy - Each patient will receive immunosuppressive chemotherapy before infusion of NK cells.

   Day -7 Cyclophosphamide at 60mg/kg Day -6 Fludarabine at 25mg/m2 daily for 5 days
2. Radiation - Each patient will receive radiation within 48 hr of NK cell infusion to make the tumor cells more sensitive to NK cell killing Radiation 2Gy
3. Cytokine support - Each pateint will receive IL-2 to support NK cell activation and expansion in vivo Day -1 alternate day for a total of 6 doses
4. NK cells - Expanded activated haploidentical NK cells will be infused on day 0.

Expanded , Activated NK cells

Bernice Oh Lingzhi, MBBS

Bernice Oh

Clarice Chan

Dario Campana

Progress in the treatment of children with leukemia and lymphoma results in high cure rates but progress in the treatment of children and adolescents with solid tumors has been slow. Despite aggressive therapy with multimodality treatment involving surgery, radiation and chemotherapy, about two thirds of the patients with metastatic Ewing sarcoma (EWS), and intermediate and high risk rhabdomyosarcoma (RMS) will relapse. The available second line therapies for relapse are limited and often not effective. There is a dire need to look for treatment options beyond conventional means for the treatment of these patients.

Infusions of allogeneic natural killer (NK) cells in leukemia patients have shown to be tolerated well without inducing graft versus host disease (GVHD). There is also mounting evidence that NK cells have activity against solid tumors.

In the lab the investigators tested NK cell activity against cell lines from different paediatric solid tumors. Among paediatric solid tumors, EWS and RMS are exquisitely sensitive to killing by expanded NK cells; NK cells also have activity against OS cells. Preliminary clinical data suggest that donor NK cells may exert antitumor activity in children with solid tumors undergoing allogeneic hematopoietic stem cell transplantation.

Taking into account the safety of adaptive NK cell infusion, and their efficacy against EWS, RMS and OS, NK cells could be a powerful new tool in the treatment of paediatric solid tumors.

The great anti-tumor activity of expanded and activated NK cells, together with the feasibility of infusing haploidentical NK cells in a non-transplant setting form a compelling rationale for the clinical testing of these NK cells in patients with sarcoma.

Adoptive transfer of allogeneic NK cells has been shown to be safe in patients with leukemia.

The patients enrolled on this will receive lymphodepleting chemotherapy with cyclophosphamide (1 day) followed by fludarabine (5 days) Each patient will receive IL-2 on alternate days starting 1 day before infusion of NK cells for a total of 6 doses.

Patient will undergo imaging MRI or PET or CT scan one month after the infusion to assess response to the NK cell infusion.

In our study we aim to determine the feasibility, safety and efficacy of expanded, activated NK cells in patients with EWS and RMS .

We will also study the persistence and phenotype of expanded NK cells in research participants with EWS and RMS .

The main hypothesis to be tested in this study is that infusion of expanded, activated haploidentical NK cells can produce measurable clinical responses in patients with EWS and RMS .

Pilot Study of Expanded , Activated Haploidentical Natural Killer Cell Infusions for Sarcomas

Radiological response will be measured based on PET or MRI or CT scan whichever is appropriate imaging for the tumor type and location.

NK cell persistence and phenotype will be monitored weekly upto 4 weeks post infusion from peripheral blood.

Patients will be monitored for toxicity based on NCI toxicity criteria CTC version 4.0

Patients performance status will be monitored using Lansky scale for patients below 16 years of age and Karnofsky performance scale for patients more than 16 years of age.

Patients will monitored for clinical evidence of GVHD

Spots Global Cancer Trial Database for expanded , activated nk cells