A Clinical Trial of Adoptive Transfer With Autologous NKT Cells in Metastatic Melanoma Patients

Study Overview
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Brief Summary
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Considerable progress in the treatment of metastatic melanoma has been made in the past 5years, with the approval of immune checkpoint-blocking antibodies and agents targeting BRAF mutation. Investigators conducted a open label, dose escalation, phase I clinical trial of to explore the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.

Detailed Description
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Considerable progress in the immunotherapy of metastatic melanoma has been made in the past 5 years, with the approval of immune checkpoint-blocking antibodies. NKT cells are a potent immunoregulatory cell population heavily implicated in promoting immunity to infection and cancer. And now with new generation of amplification method, more than 1,000 folds amplification of NKT cells can be obtained, so NKT cell based adoptive cell transfer is now available and might show its efficacy in melanoma. Investigators conducted this open label, dose escalation, phase I clinical trial of to explore the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients.

Official Title
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An Open Label, Dose Escalation, Phase I Clinical Trial of Adoptive Transfer With Autologous NKT Cells in Metastatic Melanoma Patients

Conditions
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Melanoma

Intervention / Treatment
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* Biological: NKT cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have pathological or cytologically confirmed malignant melanoma with unresectable Stage III or Stage IV (including skin and distant lymph node metastasis M1a, lung metastasis M1b). Patients who are resistant /refractory to approved therapies, or for whom no curative therapies are available. Male or female, aged ≥18 and ≤70 years; ECOG performance status score of 0-2; Life expectancy of at least six months. For women of childbearing potential, a negative pregnancy test within 7 days prior to the first treatment. At least four weeks since prior other anti-tumor therapy, including endocrine, chemotherapy/radiotherapy and targeted therapy, at least six weeks since prior nitrosourea and mitomycin dosing, and have recovered from the adverse reactions due to prior therapy. At least 4 weeks before prior surgery. Must have one measurable or evaluable lesion according to RECIST 1.1 With enough tumor tissues and diagnosed by the designated laboratory. Body weight >50kg. Without functional disorder of major organs ( laboratory examination): Neutrophils≥1.5×10^9/L, lymphocyte≥1.0×10^9/L, PLT≥100×10^9/L, Hb≥110g/L; BUN and Cr within normal range; TBIL≤1.5 times upper limit; ALT/AST≤2.5 times upper limit; PT/APTT within normal range. Without obvious hereditary disease. Must sign a written informed consent form prior to entering the study, with good compliance. Exclusion Criteria: With extrapulmonary metastatic of melanoma, for instance, distant metastasis of liver, brain, bone, adrenal gland. With serious internal disease, including serious heart disease, cerebral vascular disease, uncontrolled diabetes, uncontrolled hypertension, serious infections, active peptic ulcer, renal failure and respiratory failure. Uncontrolled infectious diseases or other serious diseases, for example, HIV, Hepatitis B and Hepatitis C. Uncontrolled brain metastases. Lymphoma or leukemia patients. Patients who have received bone marrow, stem cells or organ transplantation. With immunodeficiency or autoimmune disease, leucoderma excluded. Allergic constitution. Chronic diseases needed immunosuppressive therapy or hormone therapy. Patients treated with steroid hormone. Unable to evaluate the immune status, or patients cannot comply with follow-up clinical evaluation. Patients diagnosed with MDS (myelodysplastic syndromes). Patients who are pregnant or breast-feeding. Women (or patients' wife) of child-bearing without effective contraceptive measures. Patients receiving any investigational drug or investigational treatment within 4 weeks prior to first dosing. With uncontrolled mental disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1（NKT cells single low dose）<br>Patients will receive intravenous administration of autologous NKT cells, the dose level is 1×10^9 on d1, 2×10^9 on d3, 4×10^9 on d29, 8×10^9 on d31. | Biological: NKT cells<br>* autologous natural killer T cell<br>|
| Experimental: Arm 2（NKT cells single high dose）<br>Patients will receive intravenous administration of autologous NKT cells, the dose level is 5×10^9 on d1, 5×10^9 on d3, 5×10^9 on d29, 5×10^9 on d31. | Biological: NKT cells<br>* autologous natural killer T cell<br>|
| Experimental: Arm 3（NKT cells multiple dose）<br>Patients will receive intravenous administration of autologous NKT cells, the dose level is 5×10^9 on d1, 5×10^9 on d3 of each 28 days-cycle, the dosing will be ended after 8 cycles. | Biological: NKT cells<br>* autologous natural killer T cell<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects experiencing at least one dose limiting toxicity (DLT) of intravenous administration of autologous NKT Cells in metastatic melanoma patients. | DLT is defined as any of the following toxicities assessed as at least possibly related to NKT cells by the investigator up to 28 days each cycle(up to 8 cycles,with 28 days' safety and efficacy follow-up after the end of the last cycle) after the end of adoptive transfer: any Grade greater than or equal to (>=) 3 non-hematological toxicity, but excluding the conditions mentioned in the protocol; any Grade 4 neutropenia of greater than (>)5 days duration or Grade >=3 febrile neutropenia; any Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; any Grade 4 anemia. | 252 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NKT, metastatic melanoma