haploidentical nk cells after pemetrexed in patients with stage iv non-small cell lung cancer (nsclc)

Conditions: Non-small Cell Lung Cancer

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

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.

Eligibility criteria:
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

Keywords: non-small cell lung cancer natural killer cells hla-haploidentical family donor