Haploidentical NK Cell Infusion in Malignant Melanoma

Sponsor

Seoul National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00846833

Collaborator

(none)

Enrollment

Location

Arm

37.9

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: Haploidentical NK cell	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Feb 1, 2011

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Cyclophosphamide, high-dose interleukin-2, NK cell

Biological: Haploidentical NK cell

Collection of PBMCs by leukapheresis CD3+ depletion of apheresis product using CliniMACS®

Outcome Measures

Primary Outcome Measures

To determine the maximum-tolerated dose of haploidentical NK cells [1 year]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital	Seoul		Korea, Republic of	110-744

Sponsors and Collaborators

Seoul National University Hospital

Investigators

Principal Investigator: Dae Seog Heo, Professor, Seoul National University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT00846833

Other Study ID Numbers:

H-0808-024-253

First Posted:

Feb 19, 2009

Last Update Posted:

Jun 8, 2012

Last Verified:

Jun 1, 2012

Keywords provided by , ,

Melanoma, Experimental

Additional relevant MeSH terms:

Melanoma

Study Results

No Results Posted as of Jun 8, 2012