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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 21, 2014