Haploidentical NK Cell Infusion in Malignant Melanoma

Study Overview
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Brief Summary
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We hypothesized that haploidentical NK cells kill tumor cells more efficiently than autologous NK cells, based on the missing-self hypothesis. Therefore, we performed this study to investigate the role of haploidentical NK cell therapy in patients with refractory or relapsed malignant melanoma.

Detailed Description
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Human NK cells recognize and kill transformed cells in a MHC-unrestricted fashion, suggesting the role of cancer immunotherapy. However, autologous NK cells showed the lack of significant clinical effects, because they are inhibited by self MHC class I molecules, based on the missing-self hypothesis. Contrarily, haploidentical NK cells with KIR-ligand incompatibility can mediate graft-versus-leukemia effect and protect patients with acute myelogenous leukemia (AML) from graft-versus-host disease. In addition, adoptive transfer of haploidentical NK cells following high-intensity conditioning induced complete remission (26%) in poor-prognosis AML patients. Thus, this study was designed to investigate the role of adoptive NK cell therapy in patients with refractory or relapsed malignant melanoma using CD3+ depleting CliniMACS® system.

Official Title
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Phase I/II Study of Haploidentical Natural Killer Cell Infusion in Patients With Refractory or Relapsed Malignant Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Biological: Haploidentical NK cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic or relapsed malignant melanoma Patients who received prior chemotherapy or immunotherapy Patients who have at least one haploidentical donor willing to donate ECOG performance status 0 or 1 18 - 75 years At least one measurable disease according to the RECIST criteria Patients with 45% or more left ventricular ejection fraction Patients with 50% or more predicted DLCO Adequate bone marrow function: absolute neutrophil count ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; and hemoglobin ≥ 9 g/dL Adequate liver function: total bilirubin ≤ 1.0 x upper limit of the normal range (ULN); AST/ALT ≤ 2.5 x ULN; and alkaline phosphatase ≤ 2.5 x ULN Adequate renal function: serum creatinine ≤ 1.0 x ULN or creatinine clearance ≥ 60 mL/min/1.73m2 At least 3 months of expected survival Patients who signed informed consent Exclusion Criteria: Patients who received other chemotherapeutic agents within 30 days prior to study enrollment Patients who received adoptive cell therapy including hematopoietic stem cell transplantation Patients infected with HIV, HBV, or HCV Hypersensitivity to cyclophosphamide or interleukin-2 Patients who received organ transplantation Patients who had arrhythmia or ischemic heart disease Pregnant or lactating women Patients with uncontrolled infection who did not respond to appropriate antimicrobial agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclophosphamide, high-dose interleukin-2, NK cell<br> | Biological: Haploidentical NK cell<br>* Collection of PBMCs by leukapheresis CD3+ depletion of apheresis product using CliniMACS®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum-tolerated dose of haploidentical NK cells |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess NK cell infusion-related toxicity |  | 2 years | 
| To evaluate response rate |  | 2 years | 
| To determine immune reconstitution after NK cell infusion |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Experimental