NCT02959905

Brief Summary

The primary objective of this study is to evaluate the safety of TSA-CTL in the treatment of advanced solid tumors. The secondary objective of this study is to evaluate preliminarily the effect of TSA-CTL in the treatment of advanced solid tumors.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
11

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2016

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 21, 2016

Completed
19 days until next milestone

First Posted

Study publicly available on registry

November 9, 2016

Completed
1 month until next milestone

Study Start

First participant enrolled

December 22, 2016

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2020

Completed
1.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2022

Completed
Last Updated

February 2, 2023

Status Verified

February 1, 2023

Enrollment Period

3.7 years

First QC Date

October 21, 2016

Last Update Submit

February 1, 2023

Conditions

Keywords

Metastatic MelanomaColorectal Cancerneoantigen

Outcome Measures

Primary Outcomes (1)

  • Number of participants with adverse events as assessed by CTCAE v5.0.

    Keep records the adverse events experienced by subjects in 30 days after the first infusion.

    one month

Secondary Outcomes (4)

  • Disease Control Rate(DCR)

    one year

  • overall survival(OS)

    one year

  • progression-free survival(PFS)

    one year

  • Duration of Response(DOR)

    one year

Study Arms (3)

medium-dose lymphodepletion regimen

EXPERIMENTAL

Patients will receive medium-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL.

Biological: TSA-CTLDrug: FludarabineDrug: Cyclophosphamide

low-dose lymphodepletion regimen

EXPERIMENTAL

Patients will receive low-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL.

Biological: TSA-CTLDrug: CyclophosphamideDrug: Fludarabine

No lymphodepletion regimen

EXPERIMENTAL

Patients will only receive TSA-CTL.

Biological: TSA-CTL

Interventions

TSA-CTLBIOLOGICAL

Patients will receive TSA-CTL iv over 20-30 minutes on day 0.

Also known as: Tumor Specific Antigen Induced Cytotoxic Lymphocyte
No lymphodepletion regimenlow-dose lymphodepletion regimenmedium-dose lymphodepletion regimen

Cyclophosphamide 500 mg/m2/day iv on day -5 for one day.

Also known as: Cytoxan
low-dose lymphodepletion regimen

Fludarabine 25 mg/m2/day iv over 30 minutes on day -5 and -4 for two days.

Also known as: Fludarabine Phosphate
low-dose lymphodepletion regimenmedium-dose lymphodepletion regimen

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Greater than or equal to 18 years of age and less than or equal to 70 years of age; all genders.
  • Advanced solid tumors including but not limited to some high frequency somatic mutations, such as melanoma, colorectal cancer, gastric cancer, esophageal cancer, squamous cell carcinoma of the lung, triple-negative breast cancer, etc.
  • Advanced solid tumors patients who are HLA - A0201 /A1101/A2402 subtypes.
  • Measurable solid tumors with at least one lesion that is resectable or tumor biopsies for DNA extraction.
  • Patients who failed or were intolerant to standard treatment.
  • Patients (or their legal representatives) who are able to understand and sign the Informed Consent Form and willing to sign a durable power of attorney.
  • Clinical performance status of ECOG is 0 or 1 and expected lifetime is greater than six month and patients who are able to cooperate to observe adverse reactions and the effect of the treatment.
  • Patients of both genders must be willing to practice birth control from the time of enrollment to five months after treatment on this study.
  • Serology: HIV antibody(-), hepatitis B antigen(-), and hepatitis C antibody(-). A fertile woman must have a negative pregnancy test. Hematology: Absolute neutrophil count is greater than 1500/mm3 without the support of filgrastim; WBC is greater than or equal to 3000/mm3; lymphocyte count is greater than or equal to 800/mm3; Platelet count is greater than or equal to 100,000/mm3; Hemoglobin is greater than or equal to 9.0 g/dL ; Chemistry: Serum ALT/AST is less than or equal to 2.5 times the upper limit of normal; Serum Creatinine is less than or equal to 1.5 times the upper limit of normal ; Total bilirubin is less than or equal to 1.5 the upper limit of normal, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 times the upper limit of normal.
  • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the lymphodepletion regimen, and toxicities must have recovered to grade 1 or less (except for toxicities such as alopecia or vitiligo).
  • Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.

You may not qualify if:

  • Pregnant or lactating women.
  • Any primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • Opportunistic infection.
  • History of autoimmune disease.
  • Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system.
  • Systemic steroid therapy in the past 4 weeks.
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • Patients with unstable brain metastases.
  • Choroidal melanoma and clear cell sarcoma patients.
  • Negative for expression of MHC molecules.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510030, China

Location

Related Publications (4)

  • Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.

  • Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2.

  • Prickett TD, Crystal JS, Cohen CJ, Pasetto A, Parkhurst MR, Gartner JJ, Yao X, Wang R, Gros A, Li YF, El-Gamil M, Trebska-McGowan K, Rosenberg SA, Robbins PF. Durable Complete Response from Metastatic Melanoma after Transfer of Autologous T Cells Recognizing 10 Mutated Tumor Antigens. Cancer Immunol Res. 2016 Aug;4(8):669-78. doi: 10.1158/2326-6066.CIR-15-0215. Epub 2016 Jun 16.

  • Li D, Chen C, Li J, Yue J, Ding Y, Wang H, Liang Z, Zhang L, Qiu S, Liu G, Gao Y, Huang Y, Li D, Zhang R, Liu W, Wen X, Li B, Zhang X, Zhang X, Xu RH. A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors. Nat Commun. 2023 Jun 10;14(1):3447. doi: 10.1038/s41467-023-39225-7.

MeSH Terms

Conditions

MelanomaColorectal Neoplasms

Interventions

Cyclophosphamidefludarabinefludarabine phosphate

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Xiao Sh Zhang, Doctor

    Sun Yat-sen University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 21, 2016

First Posted

November 9, 2016

Study Start

December 22, 2016

Primary Completion

September 1, 2020

Study Completion

May 20, 2022

Last Updated

February 2, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will not share

Locations