Haploidentical NK Cell Infusion in Malignant Melanoma
June 6, 2012 updated by: Seoul National University Hospital
Phase I/II Study of Haploidentical Natural Killer Cell Infusion in Patients With Refractory or Relapsed Malignant Melanoma
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.
Study Overview
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
Enrollment (Anticipated)
12
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Seoul, Korea, Republic of, 110-744
- Seoul National University Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cyclophosphamide, high-dose interleukin-2, NK cell
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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To determine the maximum-tolerated dose of haploidentical NK cells
Time Frame: 1 year
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1 year
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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To assess NK cell infusion-related toxicity
Time Frame: 2 years
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2 years
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To evaluate response rate
Time Frame: 2 years
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2 years
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To determine immune reconstitution after NK cell infusion
Time Frame: 2 years
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2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Dae Seog Heo, Professor, Seoul National University Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
February 1, 2009
Primary Completion (Actual)
February 1, 2011
Study Completion (Actual)
April 1, 2012
Study Registration Dates
First Submitted
February 17, 2009
First Submitted That Met QC Criteria
February 18, 2009
First Posted (Estimate)
February 19, 2009
Study Record Updates
Last Update Posted (Estimate)
June 8, 2012
Last Update Submitted That Met QC Criteria
June 6, 2012
Last Verified
June 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-0808-024-253
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.