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. 2021 Dec 6;2021(12):CD011300. doi: 10.1002/14651858.CD011300.pub3

Multhoff 2020.

Study characteristics
Methods Germany; RCT; phase II
Participants Number of participants: 16 (between November 2014 and August 2017)
Number randomised

  • Experimental group (4 cycles of autologous NK cells activated ex vivo with TKD/IL‐2 after RCT (60 Gy to 70 Gy, platinum‐based chemotherapy)): 8

  • Control group (RCT alone): 8


Number evaluated

  • Age (overall): 56 to 76 years (mean 63 years)

  • Gender: male 9; female 7


Diagnosis: histologically‐proven, inoperable, clinical stage IIIa/b squamous cell lung cancer (a subtype of NSCLC)
Inclusion ‐ eligible participants 

  • First diagnosis of histologically‐proven and unresectable NSCLC with clinical stage IIIa/b

  • Completion of RCT (no longer than 1 to 2 months ago)

  • Progression‐free according to RECIST 1.1 criteria at the first assessment after RCT

  • Confirmed presence of mHsp70 on the patient's tumour, as determined by analysing circulating levels of lipid‐bound and free Hsp70 using the lipHsp70 ELISA and defined by elevated exosomal Hsp70 serum levels (above a threshold of 7.4 ng/mL)

  • Female and male patients, age 18 to 75 years

  • ECOG status ≤ 2

  • Neutrophil count ≥ 1.5 x 109/L

  • White blood cell count ≥ 2.5 x 109/L

  • Haemoglobin >10 g/L

  • Platelet count ≥ 100 x 109/L

  • Normal renal function (creatinine < 150% ULN)

  • Normal liver function (bilirubin < 200% ULN

  • G‐GT, GPT, GOT < 250% ULN)

  • Normal blood coagulation (PTT 25‐40s)

  • Measurable disease according to irRC criteria

  • Female patients of childbearing potential must have a negative pregnancy test performed during screening period (≤14 days before initiation of study drug dosing). Postmenopausal women must have been amenorrhoeal for at least 12 months to be considered of non‐childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study and for 6 months following discontinuation of the study therapy

  • Delivery of a written (signed) informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrolment and participation in the study

  • Ability to comply with study and follow‐up procedures
Interventions Experimental group: in the INT arm, patients with mHsp70‐positive tumours received TKD/IL‐2‐activated, autologous NK cells (somatic cell therapy, plasma‐derived medicinal product, IMP) subsequent to standard RCT (60 Gy to 70 Gy, platinum‐based chemotherapy). 
Control group: patients with mHsp70‐positive tumours were staged regularly at defined time intervals following standard RCT (60 Gy to 70 Gy, platinum‐based chemotherapy) in the control arm. 
Outcomes Duration of follow‐up: 18 months after randomisation, between November 2014 and August 2017

  • Progression‐free survival

  • Assessment of quality of life (QoL, QLQ‐LC13)

  • Toxicity

  • Immunobiological responses
Notes  
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Not described
Allocation concealment (selection bias) Unclear risk Not described
Blinding of participants and personnel (performance bias)
All outcomes High risk Open‐label design
Blinding of outcome assessment (detection bias)
All outcomes High risk Open‐label design
Incomplete outcome data (attrition bias)
All outcomes Low risk 13 participants were included in the analysis (81.3%)
Selective reporting (reporting bias) Low risk The prior protocol was available.
Other bias Low risk No obvious potential source of bias