Haploidentical NK Cell Infusion in Malignant Melanoma

Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00846833
• Other study ID #: H-0808-024-253
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 17, 2009
• Last updated: June 6, 2012
• Start date: February 2009
• Est. completion date: April 2012

Study information

• Verified date: June 2012
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2012
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• Haploidentical NK cell
Collection of PBMCs by leukapheresis CD3+ depletion of apheresis product using CliniMACS®

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum-tolerated dose of haploidentical NK cells		1 year	Yes
Secondary	To assess NK cell infusion-related toxicity		2 years	Yes
Secondary	To evaluate response rate		2 years	Yes
Secondary	To determine immune reconstitution after NK cell infusion		2 years	Yes