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

Phase 1

Completed

• Conditions: Non-small Cell Lung Cancer
• Interventions: Biological: Pemetrexed and donor-derived NK cell infusion

• Registration Number: NCT03366064
• Lead Sponsor: Asan Medical Center

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.

Study Timeline

• Study Start: 2017-11-09
• Study First Submitted: 2017-12-04
• Study First Submitted QC: 2017-12-04
• Study First Posted: 2017-12-08
• Primary Completion: 2018-09-03
• Study Completion: 2019-06-15
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-05
• Last Update Posted: 2019-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pemetrexed and donor NK cell infusion	Pemetrexed and donor-derived NK cell infusion	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

Primary Outcome Measures

Name	Time	Method
maximum tolerated dose of donor NK cells	6 weeks	determine the dose of NK cells that can be given within dose-limiting toxicities

Trial Locations

Locations (1)

Asan Medical Center - University of Ulsan College of Medicine; 🇰🇷 Seoul, Korea, Republic of