Haploidentical NK Cell Infusion in Malignant Melanoma

Seoul National University

Status and phase

Completed

Phase 2

Phase 1

Conditions

Melanoma

Treatments

Biological: Haploidentical NK cell

Study type

Interventional

Funder types

Other

Identifiers

NCT00846833

H-0808-024-253

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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