Haploidentical NK Cell Infusion in Malignant Melanoma

NCT ID: NCT00846833

Last Updated: 2012-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2012-04-30

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.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide, high-dose interleukin-2, NK cell

Group Type: EXPERIMENTAL

Haploidentical NK cell

Intervention Type: BIOLOGICAL

1. Collection of PBMCs by leukapheresis

2. CD3+ depletion of apheresis product using CliniMACS®

Interventions

Haploidentical NK cell

1. Collection of PBMCs by leukapheresis

2. CD3+ depletion of apheresis product using CliniMACS®

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Seoul National University Hospital

Principal Investigators

Dae Seog Heo, Professor

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

H-0808-024-253

Identifier Type: -

Identifier Source: org_study_id