Haploidentical NK Cell Infusion in Malignant Melanoma

Phase 1

Completed

• Conditions: Melanoma
• Interventions: Biological: Haploidentical NK cell

• Registration Number: NCT00846833
• Lead Sponsor: Seoul National University Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-02-17
• Study First Submitted QC: 2009-02-18
• Study First Posted: 2009-02-19
• Primary Completion: 2011-02
• Study Completion: 2012-04
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-06
• Last Update Posted: 2012-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cyclophosphamide, high-dose interleukin-2, NK cell	Haploidentical NK cell	-

Primary Outcome Measures

Name	Time	Method
To determine the maximum-tolerated dose of haploidentical NK cells	1 year

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of