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Haploidentical NK Cell Infusion in Malignant Melanoma

This study has been completed.
Sponsor:
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT00846833
First received: February 17, 2009
Last updated: June 6, 2012
Last verified: June 2012
History of Changes
  Purpose

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 Intervention Phase
Melanoma
 Biological: Haploidentical NK cell
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • To determine the maximum-tolerated dose of haploidentical NK cells [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess NK cell infusion-related toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To evaluate response rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine immune reconstitution after NK cell infusion [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 12
Study Start Date: February 2009
Study Completion Date: April 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00846833

Locations
Korea, Republic of
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
  More Information

No publications provided

Responsible Party: Dae Seog Heo/Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT00846833     History of Changes
Other Study ID Numbers: H-0808-024-253
Study First Received: February 17, 2009
Last Updated: June 6, 2012
Health Authority: South Korea: Institutional Review Board

Keywords provided by Seoul National University Hospital:
Melanoma, Experimental

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

ClinicalTrials.gov processed this record on September 26, 2012