Non-small Cell Lung Cancer
Conditions
Keywords
Non-small cell lung cancer, Natural killer cells, HLA-haploidentical family donor
Brief summary
This phase 1 trial investigate safety and maximum tolerated dose of natural killer (NK) cells derived from haploidentical family donors in patients with non-small cell lung cancer
Detailed description
Eligible patients receive pemetrexed 500 mg/m2 intravenously (Day 1). On Day 8, patients receive donor-derived NK cells via a central venous catheter. The NK cell dose is as follows; Level 1: 1.25 X 109 cells Level 2: 2.50 X 109 cells Level 3: 5.00 X 109 cells Three patients each will be treated on each dose level. Two weeks prior to donor NK cell administration to patients, HLA-haploidentical family member of the patients undergo leukapheresis after G-CSF injections to collect hematopoietic stem cells. These donor cells are then taken to the laboratory, where they were differentiated into NK cells ex vivo over approximately over 2-week period.
Interventions
BIOLOGICALPemetrexed and donor-derived NK cell infusion
Patients are administered with donor-derived NK cells one week after pemetrexed infusion
Sponsors
Korea Research Institute of Bioscience & Biotechnology
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically confirmed non-small cell lung cancer stage 4 (by AJCC 7th) * Age, 20 years of age or older * ECOG performance status, 0-2 * Life expectancy ≥3 months * Patients should have at least one measurable lesion according to RECIST Criteria v1.1 * Failure after primary systemic treatment with a regimen including platinum-containing agent (primary systemic treatment may be adjuvant chemotherapy or chemo-radiotherapy, given within 12 months) * Adequate bone marrow function (Hb ≥9 g/dL; ANC ≥1,500/uL; and platelet count ≥75,000/uL) * Adequate renal function (serum creatinine \<1 x ULN or CLcr ≥45 mL/min by Cockroft and Gault formula * Adequate liver function (total bilirubin \<1.5 x ULN; AST and ALT \<3 x ULN; and ALP \<3 x ULN, unless there is bone metastases without evidence of liver disease) * Patients should have a suitable HLA-haploidentical family member who is willing to donate hematopoietic stem cells * Patients should sign informed consent voluntarily
Exclusion criteria
* Patients who received anti-cancer chemotherapeutic or biological agents within 3 weeks. Patients who received anti-cancer treatment and did not recover from toxicities to grades 0-1 by NCI CTC AE ver 4.0 are not eligible as well. * Patients with contraindication for any medication planned to be administered in the study * Patients with significant fluid accumulation in third space (for example, pleural or pericardial effusion) that can not be controlled by drainage * Active infectious process * Inability to discontinue aspirin over 1.3 g daily or other NSAIDs. Patients cannot take aspirin or NSAIDs within 5 days of pemetrexed administration * Major surgery within 4 weeks of study participation * Palliative radiation therapy within 1 week of study participation * Acute myocardial infarction within 6 months of study participation. History of uncontrolled arrhythmia, symptomatic angina, or symptomatic heart failure * Past or current history of CNS metastasis (with exception of those patients who completed treatment of CNS metastasis and not received steroid treatment or whole brain radiotherapy within 2 weeks of screening visit or not received gamma knife treatment within 1 week of screening visit) * History of malignancy (other than skin basal cell carcinoma, carcinoma in situ of uterine cervix, or thyroid cancer) within 5 years * Pregnant or lactating women. Child-bearing women who are not willing to avoid pregnancy by contraceptives * Man not agreeing to contraceptive measures such as condom or abstinence (It is recommended that contraceptive measures be used until 6 months after pemetrexed treatment) * Other serious illness or medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximum tolerated dose of donor NK cells | 6 weeks | determine the dose of NK cells that can be given within dose-limiting toxicities |
Countries
South Korea
Outcome results
None listed