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Stage IV Gastric CarcinomaPhase 1/2NCT03044743

PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies

A Phase 1/2 study testing Fludarabine, Cyclophosphamide and Interleukin-2 in people with Stage IV Gastric Carcinoma and Stage IV Nasopharyngeal Carcinoma, run by Yang Yang at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will evaluate the safety of PD-1 knockout EBV-CTL cells in treating EBV (Epstein-Barr virus) positive advanced stage malignancies. Blood samples will also be collected for research purposes. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Fludarabine, Cyclophosphamide and Interleukin-2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesChina
Study dates
7 Apr 2017to Mar 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Pathologically verified stage IV gastric carcinoma, nasopharyngeal carcinoma and lymphoma with measurable lesions (At least one measurable lesion or the immunotherapy)
  • Pathologically verified as EBV positive malignancies
  • Human leukocyte antigen (HLA) genotypes: HLA-A02, HLA-A24 or HLA-A11 genotypes
  • Progressed after standard treatment or the patients refused to accept the standard treatment
  • Performance score: 0-1
  • Expected life span: >= 3 months
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  • Toxicities from prior treatment has resolved. Washout period is 1 months
  • Major organs function normally
  • Women at pregnant ages should be under contraception
  • Willing and able to provide informed consent

Who cannot join

  • Patients with possible drug allergy of immunotherapy
  • Patients with active bacterial or fungal infections
  • Coagulopathy, or ongoing thrombolytics and/or anticoagulation
  • Blood-borne infectious disease, e.g. hepatitis B, hepatitis C and HIV
  • History of coronary artery disease, asthma, or vascular disease or other disease inappropriate for treatment deemed by treating physician
  • With other tumors except for in situ cervical cancer, treated squamous cell carcinoma and bladder cancer (Ta and TIS) or other malignancies that have been treated with radical therapy (at least for 5 years before the enrollment)
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  • With other immune diseases, or chronic use of immunosuppressants or steroids
  • Pregnant and lactating women
  • Compliance cannot be expected
  • Other conditions requiring exclusion deemed by physician

Trial locations and contacts

2 sites in 1 country.

Baorui Liu, MD contact

0086-25-83106666-61331

baoruiliu07@163.com

Shu Su, MD contact

0086-25-83106666-61331

ssnine@126.com

China2 sites, 2 recruiting

  • The Comprehensive Cancer Center of Nanjing Drum Tower Hospital

    Nanjing, Jiangsu, 210008

    Yang Yang, MD,PhD,MSCR, 0086-18602568379, wing_young7@hotmail.com

    Jing Yan, MD, 0086-15805182426, firefreebird@163.com

    Recruiting

  • The Comprehensive Cancer Center of Nanjing Drum Tower Hospital

    Nanjing, Jiangsu, 210008

    Yang Yang, 18602568379, wing_young7@hotmail.com

    Recruiting

Other trials in China

About this study

Official title: A Phase I/II Trial of PD-1 Knockout EBV-CTLs for Advanced Stage EBV Associated Malignancies

This study will evaluate the safety of PD-1 knockout EBV-CTL cells in treating EBV (Epstein-Barr virus) positive advanced stage malignancies. Blood samples will also be collected for research purposes.

Read the detailed description

This is a study of CRISPR-Cas9 mediated PD-1 knockout-T cells from autologous origin. Patients are assigned to receive 4 circles of cell therapy. The safety and clinical response are evaluated. Biomarkers and immunological markers are also monitored.

Being tested
Fludarabine, Cyclophosphamide, Interleukin-2
Keywords
PD-1, CRISPR Cas9, EBV, advanced stage malignancies
Medical subject headings
Stomach Neoplasms, Nasopharyngeal Carcinoma, Lymphoma, T-Cell, Hodgkin Disease, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludara

    To modify immune micro-environment

  • CyclophosphamideDrug

    Also called Cytoxan

    To modify immune micro-environment

  • Interleukin-2Drug

    Also called IL-2

    To sustain the survival of infused T cells

Study groups in NCT03044743
Study groupRoleWhat they receive
PD-1 knockout EBV-CTLExperimentalPeripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISP-Cas9 system and EBV-CTL will be generated in the laboratory (PD-1 Knockout EBV-CTL). Fludarabine at 30mg/m2 and Cyclophosphamide at 300mg/m2 single dose will be administered 3 days i.v. before cell infusion. A total of 2 x 10^7/kg PD-1 Knockout CTL will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Interleukin-2 (IL-2) will be given daily( iv) since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit（IU）/day . Patients will receive a total of four cycles of treatment.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Interleukin-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients

    Measured: 6 months

Secondary outcomes (6)

  1. Response Rate

    Measured: 90 days

  2. Progression free survival (PFS)

    Measured: up to 1 year

  3. Overall Survival (OS)

    Measured: up to 3 years

  4. The duration of the normalization of tumor marker

    Measured: up to 3 years

  5. Interferon-γ change of T cells in the peripheral blood stimulated by tumor antigens

    Measured: Baseline and 1 month, 3 months and 6 months

  6. Th1/Th2 change in the peripheral blood

    Measured: Baseline and 1 month, 3 months and 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2017 (estimated)
  2. Study start7 Apr 2017
  3. Primary completionMar 2020 (estimated)
  4. Study completionMar 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03044743
Sponsor's protocol ID
PD-1-KO-EBV-CTL
Status last verified
Apr 2017
First submitted
22 Jan 2017
Last updated
2 May 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kim SY, Park C, Kim HJ, Park J, Hwang J, Kim JI, Choi MG, Kim S, Kim KM, Kang MS. Deregulation of immune response genes in patients with Epstein-Barr virus-associated gastric cancer and outcomes. Gastroenterology. 2015 Jan;148(1):137-147.e9. doi: 10.1053/j.gastro.2014.09.020. Epub 2014 Sep 22.

    PubMed 25254613

  • Quan L, Chen X, Liu A, Zhang Y, Guo X, Yan S, Liu Y. PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro. PLoS One. 2015 Sep 11;10(9):e0136476. doi: 10.1371/journal.pone.0136476. eCollection 2015.

    PubMed 26361042

  • Louis CU, Straathof K, Bollard CM, Ennamuri S, Gerken C, Lopez TT, Huls MH, Sheehan A, Wu MF, Liu H, Gee A, Brenner MK, Rooney CM, Heslop HE, Gottschalk S. Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. 2010 Nov-Dec;33(9):983-90. doi: 10.1097/CJI.0b013e3181f3cbf4.

    PubMed 20948438

  • Lloyd A, Vickery ON, Laugel B. Beyond the antigen receptor: editing the genome of T-cells for cancer adoptive cellular therapies. Front Immunol. 2013 Aug 5;4:221. doi: 10.3389/fimmu.2013.00221. eCollection 2013.

    PubMed 23935598

  • Su S, Hu B, Shao J, Shen B, Du J, Du Y, Zhou J, Yu L, Zhang L, Chen F, Sha H, Cheng L, Meng F, Zou Z, Huang X, Liu B. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep. 2016 Jan 28;6:20070. doi: 10.1038/srep20070.

    PubMed 26818188

  • Mali P, Esvelt KM, Church GM. Cas9 as a versatile tool for engineering biology. Nat Methods. 2013 Oct;10(10):957-63. doi: 10.1038/nmeth.2649.

    PubMed 24076990

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Fludarabine, Cyclophosphamide and Interleukin-2 in people with Stage IV Gastric Carcinoma and Stage IV Nasopharyngeal Carcinoma, run by Yang Yang at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Baorui Liu, MD (0086-25-83106666-61331, baoruiliu07@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03044743, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2017.

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