Malignant Sarcoma Clinical Trial
Official title:
Multicenter, Open-label, Phase I/II Clinical Trial of Infusion of Activated NK Cells for the Treatment of Children, Adolescents and Young Adults With Sarcomas
This is an exploratory therapeutic study (according to the terminology of the "ICH Harmonised Tripartite Guideline Topic E8. General Considerations for Clinical Trials". EMEA, March 1998. CPMP/ICH/291/95), open-label, non-randomized, multicenter study. It is considered phase I/II since the safety and efficacy of the infusion of allogeneic haploidentical NK cells in combination with chemotherapy and/or radiotherapy in the treatment of pediatric, adolescent and young adult patients with refractory sarcoma will be sought.
Metastatic or relapsed sarcoma in children, adolescents and young adults has a 5-year survival rate of less than 20% and current therapies, consisting of radical surgery and neoadjuvant chemotherapy, are ineffective and new therapeutic strategies are needed. Natural Killer (NK) cell therapy is a new immunotherapy in development for cancer treatment. We propose a phase I/II clinical trial with the aim of determining the safety and efficacy of infusion of activated and expanded NK cells (NKAE) from a haploidentical donor in children suffering from sarcoma refractory to conventional therapy. The study will be carried out at Hospital Universitario La Paz (Madrid), Hospital Universitario Virgen de la Arrixaca (Murcia) and Hospital Universitario Cruces (Bilbao). The results of this study are expected to have a direct influence on the approach to metastasis and refractoriness in pediatric solid tumors in future medical therapies. It is expected to recruit 10 patients who, having received conventional treatment and/or salvage, continue to present metastatic disease or progression. Each patient will receive: 1. One cycle of lymphoablative chemotherapy: cyclophosphamide 60 mg/kg iv on day -6 and fludarabine 25 mg/m2/day iv on days -5 to -1. 2. Irradiation (2Gy) localized to the tumor and/or its metastases, ideally within 48h prior to NK cell infusion. 3. NK cells: Two infusions of cells separated by at least 4 days are established. The first infusion, day 0, will infuse up to 5x107/kg cells with NK and NKT immunophenotype (CD56+CD3- and CD3+). The first infusion will ideally be performed 24-48 h after completion of immunoablative chemotherapy. The second infusion, starting at day +4, up to 5x108/kg, provided that there has been no toxicity attributable to the infusion of the cell product in the previous cycle. In no case will more than 1x107/kg immunophenotype T cells (CD56-CD3+) be infused. 4. Cytokine IL-2: Starting on day -1 IL-2 will be administered at a dose of 1x106 IU/m2 subcutaneously every 48 hours, a total of 6 doses. ;