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

Primary Purpose

Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Pemetrexed and donor-derived NK cell infusion
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Non-small cell lung cancer, Natural killer cells, HLA-haploidentical family donor

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Asan Medical Center - University of Ulsan College of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pemetrexed and donor NK cell infusion

Arm Description

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

Outcomes

Primary Outcome Measures

maximum tolerated dose of donor NK cells
determine the dose of NK cells that can be given within dose-limiting toxicities

Secondary Outcome Measures

Full Information

First Posted
December 4, 2017
Last Updated
July 5, 2019
Sponsor
Asan Medical Center
Collaborators
Korea Research Institute of Bioscience & Biotechnology
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1. Study Identification

Unique Protocol Identification Number
NCT03366064
Brief Title
Haploidentical NK Cells After Pemetrexed in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
Acronym
Medi-NK
Official Title
Phase I Trial of Haploidentical Natural Killer (NK) Cells in Combination With Pemetrexed in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
November 9, 2017 (Actual)
Primary Completion Date
September 3, 2018 (Actual)
Study Completion Date
June 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
Collaborators
Korea Research Institute of Bioscience & Biotechnology

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Non-small cell lung cancer, Natural killer cells, HLA-haploidentical family donor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pemetrexed and donor NK cell infusion
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Pemetrexed and donor-derived NK cell infusion
Intervention Description
Patients are administered with donor-derived NK cells one week after pemetrexed infusion
Primary Outcome Measure Information:
Title
maximum tolerated dose of donor NK cells
Description
determine the dose of NK cells that can be given within dose-limiting toxicities
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyoo-Hyung Lee, MD
Organizational Affiliation
University of Ulsan, Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center - University of Ulsan College of Medicine
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19881555
Citation
Yoon SR, Lee YS, Yang SH, Ahn KH, Lee JH, Lee JH, Kim DY, Kang YA, Jeon M, Seol M, Ryu SG, Chung JW, Choi I, Lee KH. Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study. Bone Marrow Transplant. 2010 Jun;45(6):1038-46. doi: 10.1038/bmt.2009.304. Epub 2009 Nov 2.
Results Reference
background
PubMed Identifier
28552421
Citation
Lee KH, Lee JH, Lee JH, Kim DY, Park HS, Choi EJ, Ko SH, Seol M, Lee YS, Kang YA, Jeon M, Baek S, Kang YL, Kim SH, Yun SC, Kim H, Jo JC, Choi Y, Joo YD, Lim SN. Reduced-Intensity Conditioning with Busulfan, Fludarabine, and Antithymocyte Globulin for Hematopoietic Cell Transplantation from Unrelated or Haploidentical Family Donors in Patients with Acute Myeloid Leukemia in Remission. Biol Blood Marrow Transplant. 2017 Sep;23(9):1555-1566. doi: 10.1016/j.bbmt.2017.05.025. Epub 2017 May 25.
Results Reference
background
PubMed Identifier
24525278
Citation
Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, Kang M, Yeom YI, Lee JL, Kim DY, Lee YS, Kang YA, Jeon M, Seol M, Lee JH, Lee JH, Kim HJ, Yun SC, Lee KH. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant. 2014 May;20(5):696-704. doi: 10.1016/j.bbmt.2014.01.031. Epub 2014 Feb 11.
Results Reference
background
PubMed Identifier
21715313
Citation
Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Hwang HJ, Jung AR, Kim SH, Yun SC, Shin HJ. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011 Sep 1;118(9):2609-17. doi: 10.1182/blood-2011-02-339838. Epub 2011 Jun 28.
Results Reference
background
PubMed Identifier
27530969
Citation
Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Kang YL, Lee JH, Lee JH, Kim DY, Lee JL, Park HS, Choi EJ, Lee YS, Kang YA, Jeon M, Seol M, Baek S, Yun SC, Kim HJ, Lee KH. Donor-Derived Natural Killer Cell Infusion after Human Leukocyte Antigen-Haploidentical Hematopoietic Cell Transplantation in Patients with Refractory Acute Leukemia. Biol Blood Marrow Transplant. 2016 Nov;22(11):2065-2076. doi: 10.1016/j.bbmt.2016.08.008. Epub 2016 Aug 12.
Results Reference
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Haploidentical NK Cells After Pemetrexed in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

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