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NCT Number: NCT02793856

PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer

This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic non-small cell lung cancer. Blood samples will also be collected for research purposes.

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Key information

Conditions

Metastatic Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

About this study

This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Pathologically verified stage IV non-small cell lung cancer with measurable lesions (On CT: longest diameter of tumoral lesion >=10 mm, shorted diameter of lymph node >=15 mm; measurable lesions should not have been irradiated)
  • Progressed after all standard treatment
  • Performance score: 0-1
  • Expected life span: >= 6 months
  • Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy
  • Major organs function normally
  • Women at pregnant ages should be under contraception
  • Willing and able to provide informed consent

Exclusion criteria

  • Pathology is mixed type
  • Emergent treatment of tumor emergency is needed
  • Poor vasculature
  • Coagulopathy, or ongoing thrombolytics and/or anticoagulation
  • Blood-borne infectious disease, e.g. hepatitis B
  • History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
  • With other immune diseases, or chronic use of immunosuppressants or steroids
  • Compliance cannot be expected
  • Other conditions requiring exclusion deemed by physician

Treatment and study plan

Cyclophosphamide

Drug

To deplete Tregs before collecting peripheral blood

Other names: Cytoxan

PD-1 Knockout T Cells

Other

Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment

Primary outcomes

  1. Number of Participants With Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of Dose of PD-1 Knockout T Cells Using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in Patients

    Time frame: Dose Escalation - Approximately 6 months

Secondary outcomes

  1. Number of Patients With Overall Response

    Time frame: 3 months

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."

  2. Number of Patients With Disease Control at 8 Weeks

    Time frame: 8 weeks

    Response will be evaluated according to RECIST v1.1 for target lesions at Week 8：Complete Response (CR), Disappearance of all extranodal target lesions; Partial Response (PR) ≥ 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Disease control = CR +PR+SD

  3. Progression Free Survival (PFS)

    Time frame: The time from the date of first edited T cell infusion to the date of disease progression or death due to any reason.

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  4. Overall Survival (OS)

    Time frame: The duration from date of first edited T cell infusion to the date of death due to any reason

    OS is defined as the time interval from date of first edited T cell infusion to the date of death due to any reason

  5. Number of Participants With Genes Mutations in Peripheral Blood Circulating Tumor DNA (ctDNA)

    Time frame: Baseline

    Driver genes mutaion stauts of Participants in ctDNA from peripheral blood were assessed by next generation sequencing (NGS), to explore the positive rate of sepicif driver genes (e.g. EGFR, ALK, ROS1, etc.) and the relationship between gene mutation status and clinical response

  6. Interleukin-6 Change in the Peripheral Blood.

    Time frame: Baseline, 1 month and 3 month

    Peripheral Interleukin-6 level at different timepoint (Baseline, 1 month and 3 month) was measured using rate nephelometry

  7. Interleukin-10 Change in the Peripheral Blood.

    Time frame: Baseline, 1 month and 3 month

    Peripheral Interleukin-10 level at different timepoint (Baseline, 1 month and 3 month) was measured using chemiluminescence.

  8. Tumor Necrosis Factor-a Change in the Peripheral Blood.

    Time frame: Baseline, 1 month and 3 month

    Peripheral Tumor Necrosis Factor-a level at different timepoint (Baseline, 1 month and 3 month) was measured using chemiluminescence.

Sponsors and collaborators

Lead sponsor

Sichuan University

Other

Collaborators

  • Chengdu MedGenCell, Co., Ltd.

Registry information

Official study title

A Phase I Clinical Trial of PD-1 Knockout Engineered T Cells Treating Patients With Advanced Non-small Cell Lung Cancer

Important dates

Study start
2016
Primary completion
2018
Study completion
2020
First posted
Jun 8, 2016
Registry last updated
Jan 12, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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