Pilot Study of Umbilical Cord Blood Natural Killer (NK) Cell Therapy for Pediatric Neuroblastoma.
Overview
- Phase
- Phase 1
- Intervention
- umbilical cord blood NK cells
- Conditions
- Neuroblastoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- To evaluate the safety and tolerability of umbilical cord blood natural killer cell injection in combination with other treatments of high-risk, recurrent/refractory neuroblastoma in children
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Neuroblastoma is the most common extracranial solid tumor, with more than half of the patients diagnosed at the metastatic stage, classified as high-risk. High-risk neuroblastoma has a poor prognosis and low survival rate. Despite treatment with induction, consolidation, and maintenance therapy including GD2 monoclonal antibody, the survival rate is only about 60%, and many patients still relapse, progress, and die.
NK cell therapy is an emerging immunotherapy that can effectively inhibit and kill tumor cells without significant adverse reactions, reducing the risk of tumor recurrence and metastasis, and improving patients' immunity and quality of life. Its safety has been widely recognized. Currently, clinical trials of NK cell infusion therapy for neuroblastoma patients are ongoing, and NK cell-based immunotherapy holds great clinical promise for neuroblastoma. We plan to conduct a phase I clinical trial on umbilical cord blood NK cell therapy in combination with other treatments (GD2 antibody, chemotherpay, etc) for high-risk, recurrent/refractory neuroblastoma in children to determine the maximum tolerated dose of umbilical cord blood NK cell therapy in these patients, thereby laying the foundation for future combination therapies and phase II and III clinical studies.
Detailed Description
To improve the prognosis of high-risk, Recurrent/Refractory neuroblastoma, we conducted a prospective Phase I clinical trial. Patients with high-risk and Recurrent/Refractory neuroblastoma who had undergone multidisciplinary treatment received umbilical cord blood NK cell infusions. The safety and efficacy of umbilical cord blood NK cells in combination with other therapy (GD2 antibody, chemotherpay, etc) were evaluated.
Investigators
Yizhuo Zhang
Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •All of the following criteria must be met in order to be eligible for this trial:
- •Agree to participate in the trial and sign a written informed consent form;
- •Age ≤18 years, gender not limited;
- •Karnofsky (≥16 years old) or Lansky (\<16 years old) physical status score (Appendix II) of at least 50;
- •Patients diagnosed with high-risk, recurrent/refractory neuroblastoma in children according to clinical diagnostic criteria, who have undergone comprehensive treatment (surgery, chemotherapy, radiotherapy ± stem cell transplantation ± GD2 monoclonal antibody therapy);
- •Expected survival period of at least 12 weeks;
- •The patient must have fully recovered from the acute toxic effects of all previous anticancer chemotherapy, such as recovery to grade I after bone marrow suppression;
- •Bone marrow suppressive chemotherapy: At least 21 days after the last bone marrow suppressive chemotherapy (if nitrosoureas were used previously, then 42 days);
- •Investigational drugs or anticancer therapies other than chemotherapy: Must not be used within 28 days before the planned start of NK cell immunotherapy. Full recovery from the clinically significant toxicity of that therapy must be confirmed;
- •Hematopoietic growth factors: At least 14 days after the last dose of long-acting growth factors or 3 days after the last dose of short-acting growth factors;
Exclusion Criteria
- •Patients who meet any of the following criteria are not eligible for this trial:
- •Symptomatic brain metastases (patients whose brain metastases have been treated and whose symptoms have been stable for more than two months prior to enrollment may be enrolled, but must be confirmed by cranial MRI, CT, or venography as having no symptoms of cerebral hemorrhage);
- •Suffering from the following cardiovascular diseases: grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms for males and ≥470 ms for females); according to the NYHA standard (Appendix Three), class III-IV heart failure, or echocardiography indicating left ventricular ejection fraction (LVEF) \<50%;
- •Having a history of interstitial lung disease or suffering from interstitial lung disease at the same time;
- •Coagulation disorders (INR \>1.5 or prothrombin time (PT) \>ULN +4 seconds or APTT \>1.5 ULN), with a tendency to bleed or currently receiving thrombolytic or anticoagulant therapy;
- •Arterial/venous thromboembolic events occurring within 12 months before enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- •Known hereditary or acquired bleeding and thrombosis tendencies (such as hemophilia patients, coagulation disorders, thrombocytopenia, splenomegaly, etc.);
- •Long-term unhealed wounds or fractures (except pathological fractures caused by tumors);
- •Receiving major surgery or experiencing severe traumatic injuries, fractures, or ulcers within 4 weeks before enrollment;
- •Factors significantly affecting the absorption of oral medications, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
Arms & Interventions
Treatment with umbilical cord blood NK cells
All subjects will receive Ex vivo Expanded and activated umbilical cord blood NK cells infusion.
Intervention: umbilical cord blood NK cells
Outcomes
Primary Outcomes
To evaluate the safety and tolerability of umbilical cord blood natural killer cell injection in combination with other treatments of high-risk, recurrent/refractory neuroblastoma in children
Time Frame: One weeks after the first cycle (each cycle is 28 days)
According to the '3+3' design principle, the Maximum Tolerated Dose (MTD) is determined. Adverse events observed during the trial are graded according to the NCI CTCAE 5.0 criteria. Adverse events related to the drug (definitely related, probably related, or possibly related) occurring within 36 days after the first infusion of umbilical cord blood NK cells (during the first cycle) are considered as Dose-Limiting Toxicity (DLT). The definitions of DLT include: (1) Hematological toxicity: Grade 4 neutropenia lasting ≥7 days; Grade 4 thrombocytopenia lasting ≥7 days; (2) Grade 3/4 non-hematological toxicities (excluding nausea, vomiting, and alopecia); (3) Any toxicity leading to a delay in chemotherapy for more than 2 weeks.
Secondary Outcomes
- overall response rate (ORR) after 2 courses of umbilical cord blood natural killer cell infusion(Two weeks after the second cycle (a total of 16 weeks after the strart of first umbilical cord blood natural killer cell infusion))