Phase I Study of Umbilical Cord Blood Natural Killer (NK) Cell Therapy for Children With High-risk, R/R Neuroblastoma.

NCT06631391 | Recruiting Phase 1 DMC

• 1 other identifier: UCBNK01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Neuroblastoma

Keywords

neuroblastoma, umbilical Cord blood NK cells

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  One weeks after the first cycle (each cycle is 28 days)

Secondary Outcomes (1)

• 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)

Study Arms (1)

Treatment with umbilical cord blood NK cells

EXPERIMENTAL

All subjects will receive Ex vivo Expanded and activated umbilical cord blood NK cells infusion.

Biological: umbilical cord blood NK cells

Interventions

umbilical cord blood NK cells BIOLOGICAL

This is a phase I prospective clinical trial, including phase Ia and phase Ib. Phase Ia include 3 dose levels, utilizing a 3+3 design principle, and each dose level will enroll at least 3 subjects. The recommended dose for phase Ia was used in phase Ib. Each patient receives two courses of umbilical cord blood NK cell therapy (a total of 8 infusions of umbilical cord blood NK cells) and other therapy.

Treatment with umbilical cord blood NK cells

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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;
• X-ray therapy (XRT): At least 14 days after local palliative XRT (small field port); if other substantial bone marrow (BM) irradiation is involved, including prior radioactive iodine metaiodobenzylguanidine (131I-MIBG) treatment, it must end at least 42 days ago;
• Stem cell infusion without total body irradiation (TBI): No active graft-versus-host disease, must have ended at least 56 days after transplantation or stem cell infusion;
• Laboratory tests during the screening period must meet the following conditions:
• Absolute neutrophil count (ANC) ≥1.0×10\^9/L (if bone marrow involvement, then ANC ≥0.5×10\^9/L)
• Platelet count (PLT) ≥75×10\^9/L (if bone marrow involvement, then PLT ≥20×10\^9/L)

You may not qualify if:

• 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;
• Experiencing abdominal fistula, gastrointestinal perforation, or abdominal abscess within 6 months before enrollment;
• Routine urine tests showing proteinuria ≥ +, and confirmed 24-hour urine protein quantification ≥1.0 g;
• Symptomatic serosal effusions requiring symptomatic treatment (including pleural effusion, ascites, pericardial effusion); Note: Asymptomatic serosal effusions can be enrolled, symptomatic serosal effusions after active symptomatic treatment (anticancer drugs cannot be used for treating serosal effusions), judged by the investigator to meet the enrollment criteria can be enrolled;
• Active infections requiring antimicrobial treatment (e.g., needing antibacterial drugs, antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungal drug treatment);
• History of psychoactive substance abuse that cannot be quit or has mental disorders;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

NOT YET RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Yizhuo Zhang

  SunYat Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yizhuo zhang

CONTACT

020-87342460; zhangyzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: To evaluate the safety, tolerability and efficacy of umbilical cord blood natural killer cell injection in combination with other treatments (GD2 antibody, chemotherpay, etc) in high-risk, recurrent/refractory neuroblastoma in children

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 8, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2029
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

CN (2)