Clinical trial NCT00846833: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: Melanoma, Experimental
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2009-02-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To determine the maximum-tolerated dose of haploidentical NK cells
timeFrame: 1 year
Secondary outcomes:
measure: To assess NK cell infusion-related toxicity
timeFrame: 2 years
measure: To evaluate response rate
timeFrame: 2 years
measure: To determine immune reconstitution after NK cell infusion
timeFrame: 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Dae Seog Heo, Professor
role: PRINCIPAL_INVESTIGATOR
References: