Treatment of Relapsed or Refractory Epstein-Barr Virus Positive T-cell Lymphoma With hNeo-T

NCT06224049 | Recruiting Early Phase 1 DMC

• 2 other identifiers: BGI-006KYLLHS-20230102C
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To evaluate the safety and tolerability of hNeo-T injection in patients with relapsed or refractory EBV-positive T-cell lymphoma. Secondary objective: To evaluate the effectiveness of hNeo-T injection, and to evaluate the objective response rate (ORR) and disease control rate (DCR) by Lugano2014 criteria; Progression-free survival (PFS), duration of response (DOR), and overall survival (OS ) followed. Objective of the exploratory study: To investigate the in vivo process of hNeo-T injection and describe the activity and related biological functions of hNeo-T cells in vivo, including but not limited to.

Conditions

T-cell Lymphoma

Keywords

T-cell lymphomas; Epstein-Barr Virus; hNeo-T

Outcome Measures

Primary Outcomes (1)

• Safety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)

  To determine the incidence of AE and SAE in clinical trials

  The first dose will be administered until 28 days after the last dose

Secondary Outcomes (5)

• Objective response rate (ORR)

  Up to 48 weeks

• Disease control rate (DCR)

  Up to 48 weeks

• Progression free survival (PFS)

  Up to 52 weeks

• Duration of response (DOR)

  Up to 36 weeks

• Overall survival (OS)

  Up to 72 weeks

Study Arms (1)

hNeo-T

EXPERIMENTAL

The escalating doses of hNeo-T in this study will be 5\*10\^7 cells and1\*10\^8 cells.

Biological: hNeo-T; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

hNeo-T BIOLOGICAL

After subject screening, peripheral blood mononuclear cell （PBMC） donors matching half or more of the subject's HLA matching will undergo blood collection to prepare hNeo-T. hNeo-T preparation is expected to be 25-30 days after blood collection. In this study, the bridging therapy will be allowed before Chemotherapy preconditioning, and the investigators will decide whether to use it. Chemotherapy preconditioning will be performed before hNeo-T transfusion. If the absolute value of lymphocyte (LYM) before pretreatment is \<0.8×10\^9/L and the subject meets the criteria for cell transfusion, the chemotherapy preconditioning will not be performed and subsequent cell transfusion can be performed directly.

hNeo-T

Cyclophosphamide DRUG

Chemotherapy preconditioning will be performed before hNeo-T transfusion.

hNeo-T

Fludarabine DRUG

Chemotherapy preconditioning will be performed before hNeo-T transfusion

hNeo-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, and ≤75 years old, gender is not limited;
• Must have histologically or cytologically confirmed T-cell lymphoma with at least one measurable tumor lesion (according to Lugano2014 criteria);
• The subject's HLA type is HLA-A0201/1101/2402/0203 (containing at least one of the subtypes, as determined by the test report issued by the central laboratory), and there is at least one healthy donor who is a semi-matching HLA type or more with the subject. At least one of the HLA matching loci is HLA-A0201/1101/2402/0203；
• The subject has been previously determined to be EBV positive or has been determined to be EBV positive after testing;
• The subject has paraffin-embedded tumor tissue/section or biopsy tumor tissue within 2.5 years (tissue biopsy is recommended for subjects with easy-to-sample tumor lesions and consent to biopsy), and these tissues are qualified by gene sequencing data. And the tumor neoantigen screening qualified;
• Disease progression after adequate first-line systemic treatment, or disease progression ≥2 cycles (PD) after first-line or above systemic systemic treatment, or ≥4 cycles without remission (CR or PR). Remarks: The first-line systemic treatment should refer to the latest version of the "Lymphoma Diagnosis and Treatment Guide" issued by China's "Chinese Society of Clinical Oncology".
• Volunteer to participate in clinical studies; I or legal guardian fully understand and know the study and sign the informed consent; Willing to follow and be able to complete all test procedures;
• ECOG score ≤1 score;
• Have venous access to meet venous blood collection;
• The survival time is expected to be ≥6 months;
• The subjects are willing to use a reliable method of contraception during treatment and within 3 months after the end of treatment, and the blood pregnancy test of women of childbearing age is negative;
• Laboratory test results and vital organ functions meet the following requirements: 1) \*HIV antibody negative; No active syphilis infection; Negative antibodies to hepatitis C virus; HBV DNA detection value is lower than the upper limit of normal value; 2) Blood routine: absolute value of neutrophil (ANC) ≥1×10\^9/L, platelet count (PLT) ≥75×10\^9/L, hemoglobin concentration (HGB) ≥80g/L; 3) Blood biochemistry: glutamic-pyruvic transaminase (ALT) and glutamic-oxalic transaminase (AST) ≤3 times the upper limit of normal (ULN) (ALT and AST≤5 times ULN in liver metastasis subjects); Serum creatinine ≤1.5 ULN; Total bilirubin ≤1.5 ULN, or total bilirubin \<3 ULN for subjects with GilbertsSyndrome; 4) Coagulation function: prothrombin time (PT) and International standard ratio (INR) ≤1.5 times ULN, activated partial thromboplastin time (APTT) ≤1.5 times ULN (for subjects taking anticoagulant drugs for a long time, the coagulation related indexes can meet the normal value range after medication); 5) Left ventricular ejection fraction (LVEF) ≥50%;
• Before administration with Chemotherapy preconditioning: 1) Any chemotherapy, targeted drugs, immune checkpoint inhibitors, other drugs studied in clinical trials, Chinese medicines with anti-tumor indications, and other anti-tumor treatments received have passed the 4-week washout period, and the toxic side effects have returned to grade 1 or lower (excluding hair loss, vitiligo, and other events that the investigator has judged to be tolerated); 2) If major surgery is performed within 3 weeks, adverse reactions have recovered to grade 1 or lower.

You may not qualify if:

• Pregnant or lactating women;
• People with a history of severe hypersensitivity to the cells used in this study and to any drugs;
• Patients with a history of organ transplantation, excluding hematopoietic stem cell transplantation;
• History of allogeneic hematopoietic stem cell transplantation; Acute or chronic graft-versus-host disease (GVHD);
• Clear central nervous system involvement of lymphoma, including parenchyma, meningeal invasion or spinal cord compression;
• Any person with active autoimmune disease or who has a history of autoimmune disease that the investigator has determined to be ineligible for this study, including but not limited to the following diseases: Such as systemic lupus erythematosus, immune-related neuropathy, multiple sclerosis, Guillain-Barre syndrome, myasthenia gravis, connective tissue diseases, inflammatory bowel diseases including Crohn's disease and ulcerative colitis (except for patients with vitiligo, eczema, type I diabetes, rheumatoid arthritis and other joint diseases, sjogren's syndrome and psoriasis controlled with topical drugs);
• Uncontrolled concomitant or infectious diseases, such as acutely active infected persons requiring systemic antibiotic, antiviral or antifungal treatment within 2 weeks prior to enrollment;
• Subjects who were scheduled to receive glucocorticoids (prednisone or equivalent dose \>10mg/ day) or other immunosuppressants for a condition within 2 weeks prior to lymphocyte clearance preconditioning administration and during the study period were excluded. Remarks: In the absence of active autoimmune disease, prednisone or an equivalent adrenal drug dose ≤10mg/ day is allowed to substitute administration; Subjects were allowed to use topical, ocular, intraarticular, intranasal, and inhaled corticosteroids (with very low systemic absorption);
• Subject is scheduled to receive immunomodulatory drugs (such as interferon, GM-CSF, thymosin, gamma globulin, etc.) within 2 weeks before lymphocyte clearance preconditioning administration and during the study period due to certain conditions;
• The investigator evaluates that the subject is unable or unwilling to comply with the requirements of the study protocol;
• Those with functional defects of genes related to antigen presentation, antigen recognition and cell killing detected by sequencing;
• History of other malignant tumors within the past 5 years; Excluding curable basal or squamous cell skin cancer, superficial bladder or prostate carcinoma in situ, cervical carcinoma in situ or breast carcinoma in situ;
• The subject has any disease or medical condition that may affect the evaluation of the safety or efficacy of the investigational drug.

Sponsors & Collaborators

• BGI, China: lead
• Shenzhen University General Hospital: collaborator

Study Sites (1)

ShenZhen University General Hospital

Shenzhen, Guangdong, 518000, China

RECRUITING

Related Publications (5)

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  PMID: 27927646 BACKGROUND

• Chen Y, Zhao H, Luo J, Liao Y, Dan X, Hu G, Gu W. A phase I dose-escalation study of neoantigen-activated haploidentical T cell therapy for the treatment of relapsed or refractory peripheral T-cell lymphoma. Front Oncol. 2022 Nov 10;12:944511. doi: 10.3389/fonc.2022.944511. eCollection 2022.

  PMID: 36439517 BACKGROUND

• Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018 Jun;24(6):724-730. doi: 10.1038/s41591-018-0040-8. Epub 2018 Jun 4.

  PMID: 29867227 BACKGROUND

• Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, Shukla SA, Hu Z, Li L, Le PM, Allesoe RL, Richman AR, Kowalczyk MS, Abdelrahman S, Geduldig JE, Charbonneau S, Pelton K, Iorgulescu JB, Elagina L, Zhang W, Olive O, McCluskey C, Olsen LR, Stevens J, Lane WJ, Salazar AM, Daley H, Wen PY, Chiocca EA, Harden M, Lennon NJ, Gabriel S, Getz G, Lander ES, Regev A, Ritz J, Neuberg D, Rodig SJ, Ligon KL, Suva ML, Wucherpfennig KW, Hacohen N, Fritsch EF, Livak KJ, Ott PA, Wu CJ, Reardon DA. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019 Jan;565(7738):234-239. doi: 10.1038/s41586-018-0792-9. Epub 2018 Dec 19.

  PMID: 30568305 BACKGROUND

• Hilf N, Kuttruff-Coqui S, Frenzel K, Bukur V, Stevanovic S, Gouttefangeas C, Platten M, Tabatabai G, Dutoit V, van der Burg SH, Thor Straten P, Martinez-Ricarte F, Ponsati B, Okada H, Lassen U, Admon A, Ottensmeier CH, Ulges A, Kreiter S, von Deimling A, Skardelly M, Migliorini D, Kroep JR, Idorn M, Rodon J, Piro J, Poulsen HS, Shraibman B, McCann K, Mendrzyk R, Lower M, Stieglbauer M, Britten CM, Capper D, Welters MJP, Sahuquillo J, Kiesel K, Derhovanessian E, Rusch E, Bunse L, Song C, Heesch S, Wagner C, Kemmer-Bruck A, Ludwig J, Castle JC, Schoor O, Tadmor AD, Green E, Fritsche J, Meyer M, Pawlowski N, Dorner S, Hoffgaard F, Rossler B, Maurer D, Weinschenk T, Reinhardt C, Huber C, Rammensee HG, Singh-Jasuja H, Sahin U, Dietrich PY, Wick W. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019 Jan;565(7738):240-245. doi: 10.1038/s41586-018-0810-y. Epub 2018 Dec 19.

  PMID: 30568303 BACKGROUND

MeSH Terms

Conditions

Lymphoma, T-Cell; Epstein-Barr Virus Infections

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• LiXin Wang, Doctor

  Shenzhen University General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

LiXin Wang, Doctor

CONTACT

13718000488; Wanglixin1991@sohu.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: January 25, 2024
• Study Start: December 1, 2023
• Primary Completion: June 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)