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Haploidentical NK Cell Infusion in Malignant Melanoma

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Haploidentical NK cell
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, Experimental

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Seoul National University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cyclophosphamide, high-dose interleukin-2, NK cell

Arm Description

Outcomes

Primary Outcome Measures

To determine the maximum-tolerated dose of haploidentical NK cells

Secondary Outcome Measures

To assess NK cell infusion-related toxicity
To evaluate response rate
To determine immune reconstitution after NK cell infusion

Full Information

First Posted
February 17, 2009
Last Updated
June 6, 2012
Sponsor
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00846833
Brief Title
Haploidentical NK Cell Infusion in Malignant Melanoma
Official Title
Phase I/II Study of Haploidentical Natural Killer Cell Infusion in Patients With Refractory or Relapsed Malignant Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Seoul National University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Melanoma, Experimental

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cyclophosphamide, high-dose interleukin-2, NK cell
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Haploidentical NK cell
Intervention Description
Collection of PBMCs by leukapheresis CD3+ depletion of apheresis product using CliniMACS®
Primary Outcome Measure Information:
Title
To determine the maximum-tolerated dose of haploidentical NK cells
Time Frame
1 year
Secondary Outcome Measure Information:
Title
To assess NK cell infusion-related toxicity
Time Frame
2 years
Title
To evaluate response rate
Time Frame
2 years
Title
To determine immune reconstitution after NK cell infusion
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dae Seog Heo, Professor
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of

12. IPD Sharing Statement

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Haploidentical NK Cell Infusion in Malignant Melanoma

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