Safety and efficacy evaluation of using natural killer cells to treat patients with recurrent and refractory high-risk neuroblastoma
- Conditions
- recurrent and refractory of high-risk neuroblastoma.adrenal gland, Cancer, neuroblastomaC74.90
- Registration Number
- IRCT20170122032121N8
- Lead Sponsor
- Kian immune cell company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 10
High-risk neuroblastoma that is resistant to standard induction therapy based on COG (Children’s Oncology Group) criteria (according to INRG criteria and having received at least 4 cycles of multi-drug induction chemotherapy, and not responding to conventional treatments).
Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem cell transplantation or aggressive therapy.
A minimum life expectancy of 6 months.
Patients must have a pathological diagnosis of neuroblastoma and/or confirmation of tumor cells in the bone marrow with increased urinary catecholamines.
Measurable residual disease based on imaging findings using Curie scoring or MIBG or PET imaging criteria (1: measurable tumor of at least 10 mm in one dimension on MRI or CT scan with positive uptake on I-123 MIBG scan (MIBG avid”) or 2) increased FDG uptake on 18F-FDG PET-CT or PET-MRI (PET avid”)).
Insufficient bone marrow function: Platelet count > 50,000/µL, independent of transfusion (no platelet transfusion within one week).Absolute neutrophil count (ANC) maximum of 500 per microliter.Hemoglobin > 10 grams per deciliter.
Insufficient liver function: Plasma bilirubin level more than 1.5 times the upper limit of normal (ULN).SGPT (ALT) at least three times the upper limit of normal (a level of 45 units per liter is considered the upper limit of normal).
Insufficient kidney function: Creatinine clearance or estimated radioisotope GFR < 70 ml/min/1.73m².Plasma creatinine level more than 1.5 times the upper limit of normal based on age/gender.
Insufficient central nervous system functionIf seizures are present, entry into the study is not possible if seizures are not well controlled with anticonvulsant drugs.CNS toxicity > Grade 2.
Insufficient cardiovascular functionShortening fraction < 27% by ECHO OREjection fraction < 50% by ECHO or gated radionuclide study.
Insufficient pulmonary functionEvidence of dyspnea at rest.Exercise intolerance.Chronic need for oxygen and room air pulse oximetry < 94% if pulse oximetry evaluation is clinically indicated.Presence of current pleural or pericardial effusion.
Inability to tolerate new treatment due to emergency conditions.
Elevated catecholamines (more than twice the ULN) or sole involvement of bone marrow (bone marrow positive for NB as the only evaluable disease without confirmatory pathology report).
Receiving 0.5 mg/kg/day of systemic steroids (equivalent to prednisone) for at least 7 days before enrollment.
Receiving CYP3A4 inducers or inhibitors at least 7 days before study enrollment.
Diagnosis of any other malignancy alongside the diagnosis of neuroblastoma.
Diarrhea > Grade 2 (4 to 6 stools per day).
Significant illness not covered by exclusion criteria but interfering with the study process or increasing the intensity of treatment with NK cells.
Participation in another clinical trial.
Severe impairment of major organ functions, such as renal, cardiac, hepatic, neurological, pulmonary, or gastrointestinal toxicity above Grade 2 according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 5.0 (CTC v5.0).
Inability to comply with protocol requirements.
Lack of confirmed and signed consent by the patient's guardians.
Evidence of HIV disease (Human Immunodeficiency Virus) or positive serology for HIV.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety. Timepoint: After each injection to next injection and 2 weeks after last injection. Method of measurement: Using CTCAEs (Common Terminology Criteria for Adverse Events) checklist.
- Secondary Outcome Measures
Name Time Method Response rate comparison between control and intervention groups. Timepoint: 6 and 12 months after the last injection. Method of measurement: MRI and MIBG or PET scan.;Overall survival and progression-free survival. Timepoint: up to 12 months after the last injection. Method of measurement: using Kaplan-Meier method.;Alteration in bone marrow sample. Timepoint: 12 months after the last injection. Method of measurement: Bone marrow aspiration and H&E staining.