Haploidentical NK Cell Infusion in Malignant Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00846833
Recruitment Status : Completed
First Posted : February 19, 2009
Last Update Posted : June 8, 2012
Information provided by:
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.

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
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 : February 2009
Actual Primary Completion Date : February 2011
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

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

Primary Outcome Measures :
  1. To determine the maximum-tolerated dose of haploidentical NK cells [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. To assess NK cell infusion-related toxicity [ Time Frame: 2 years ]
  2. To evaluate response rate [ Time Frame: 2 years ]
  3. To determine immune reconstitution after NK cell infusion [ Time Frame: 2 years ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00846833

Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Seoul National University Hospital
Principal Investigator: Dae Seog Heo, Professor Seoul National University Hospital

Responsible Party: Dae Seog Heo/Professor, Seoul National University Hospital Identifier: NCT00846833     History of Changes
Other Study ID Numbers: H-0808-024-253
First Posted: February 19, 2009    Key Record Dates
Last Update Posted: June 8, 2012
Last Verified: June 2012

Keywords provided by Seoul National University Hospital:
Melanoma, Experimental

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas