Pilot Study of Expanded , Activated Haploidentical Natural Killer Cell Infusions for Sarcomas (NKEXPSARC)
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|ClinicalTrials.gov Identifier: NCT02409576|
Recruitment Status : Recruiting
First Posted : April 7, 2015
Last Update Posted : November 6, 2017
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), metastatic osteosarcoma (OS) 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.
|Condition or disease||Intervention/treatment||Phase|
|Ewing Sarcoma Osteosarcoma Rhabdomyosarcoma||Biological: Expanded , Activated NK cells||Phase 1 Phase 2|
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, RMS and OS.
We will also study the persistence and phenotype of expanded NK cells in research participants with EWS, RMS and OS.
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, RMS and OS.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Expanded , Activated Haploidentical Natural Killer Cell Infusions for Sarcomas|
|Study Start Date :||February 2015|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||September 2018|
Experimental: Expanded, activated NK Cells(NKEXPSARC)
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.
Biological: Expanded , Activated NK cells
- Disease response after expanded activated NK cell infusion [ Time Frame: 1 month post-NK cell infusion (and at regular intervals thereafter till a year post-NK cell infusion) ]Radiological response will be measured based on PET or MRI or CT scan whichever is appropriate imaging for the tumor type and location.
- Persistence and phenotype of expanded NK cells in research participants with EWS, RMS and OS. [ Time Frame: 1 month ( 30 days) post- NK cell infusion ]NK cell persistence and phenotype will be monitored weekly upto 4 weeks post infusion from peripheral blood.
- Toxicity of NK cells infusion (NCI toxicity criteria CTC version 4.0) [ Time Frame: 1 month ( 30 days) post- NK cell infusion ]Patients will be monitored for toxicity based on NCI toxicity criteria CTC version 4.0
- Performance status will be assessed by age-dependent Performances Scores ( Lansky scale or Karnofsky performance scale) [ Time Frame: Initiation of conditioning till 30 days post-NK cell infusion ]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.
- Acute and Chronic GVHD [ Time Frame: Initiation of conditioning until 1 month ( 30 days) post- last dose of IL-2 ]Patients will monitored for clinical evidence of GVHD
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02409576
|Contact: Chetan Dhamne, MBBS||(65)6772 firstname.lastname@example.org|
|National University Hospital||Recruiting|
|Singapore, Singapore, 119228|
|Contact: Chetan Dhamne (65) 6772 3361 email@example.com|
|Contact: Clarice Chan (65) 67726586 firstname.lastname@example.org|
|Principal Investigator: Chetan Dhamne|
|Sub-Investigator: Dario Campana|
|KK Women's and Children's Hospital||Not yet recruiting|
|Contact: Tan Ah Moy email@example.com|
|Contact: Jillian Teo +65 6394-5025 Jillian.Teo.CL@kkh.com.sg|
|Principal Investigator:||Chetan Dhamne||Department of Paediatrics, National University Hospital|
|Principal Investigator:||Dario Campana||Department of Paediatrics, National University of Singapore|