Haploidentical NK Cells After Pemetrexed in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Trial of Haploidentical Natural Killer (NK) Cells in Combination With Pemetrexed in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: Pemetrexed and donor-derived NK cell infusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed and donor NK cell infusion<br>Eligible patients with stage 4 non-small cell lung cancer receive NK cells derived from HLA-haploidentical family donors. One week prior to NK cell infusion, patients receive pemetrexed (500 mg/m2) intravenous infusion | Biological: Pemetrexed and donor-derived NK cell infusion<br>* Patients are administered with donor-derived NK cells one week after pemetrexed infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose of donor NK cells | determine the dose of NK cells that can be given within dose-limiting toxicities | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, Natural killer cells, HLA-haploidentical family donor