A Phase I/II Single-center Study Evaluating the Safety and Efficacy of BCOR and ZC3H12 Genes Knock-out CD19-targeting CAR-T Cell Therapy in Adults With Refractory/Relapsed Refractory/Relapsed B-cell Lymphoma

Status: Recruiting
Location: See location...
Intervention Type: Biological, Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

In this single-center, single-arm, prospective, Phase 1/2 study, the safety and efficacy of autologous BCOR and ZC3H12 genes knock-out CD19-targeting chimeric antigen receptor (CAR) T-cell therapy will be evaluated in patients with refractory/relapsed (r/r) B-cell Lymphoma. For simplicity, we have termed these CD19 CAR T cells lacking ZC3H12A and BCOR as CAR19TIF( immortal-like and functional CD19 CAR T ) cells, reflecting their immortal-like and functional characteristics. In phase 1, 3 eligible patients will be enrolled and receive CAR19TIF cells at a initial dose of 5×10\^5 cells/kg. Based on the results, subsequently an additional 3-15 patients will be enrolled in a 3+3 dose-escalation/decline design to adjust the dose of CAR19TIF cells to achieve optimal safety and efficacy. The recommended Phase 2 dose (RP2D) will then be established. 10 to 12 subjects will be enrolled and receive CAR19TIF cells infusion at dose of RP2D.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 70
Healthy Volunteers: f
View:

• Age 18-70 (inclusive).

• Subjects who meet the following requirements:

‣ 1 Histologically confirmed refractory/relapsed B cell Non-Hodgkin's lymphomas (NHL), including the following types defined by World Health Organization (WHO) 2016:

⁃ Diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS);

⁃ Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);

⁃ Transformed follicular lymphoma (TFL);

⁃ High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBCL);

⁃ Follicular lymphoma (FL);

⁃ Mantle cell lymphoma (MCL) (pathologically confirmed, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1);

⁃ Marginal zone lymphoma (MZL), including nodal or splenic marginal zone B-cell lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma.

‣ 2 Relapsed disease is defined as disease progression (PD) after achieving disease remission (including CR and PR) with the latest standard regimen.

‣ 3 Refractory disease is defined as no CR to first-line therapy: Evaluation of PD (never reached response or SD) after standard first-line treatment, or

⁃ SD as best response after at least 4 cycles of first-line therapy (eg,4 cycles of R-CHOP), or

⁃ PR as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 6 months of therapy, or

⁃ Refractory post-autologous stem cell transplant (ASCT): i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals); ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy.

‣ 4 Individuals who are intolerant to standard treatment can also be included in the study in the investigator's judgment.

• Individuals must have received adequate prior therapy:

‣ 1 For MCL, prior therapy must have included:

⁃ Anthracycline or bendamustine-containing chemotherapy and

⁃ Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and

⁃ Bruton's tyrosine kinase inhibitor (BTKi). 3.2 For other types, prior therapy must have included:

⁃ Anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and

⁃ Anthracycline containing chemotherapy regimen. 3.3 For individual with transformed FL must have relapse or refractory disease after transformation to DLBCL.

• At least 1 measurable lesion: lymph node site with a long axis \>1.5cm, extranodal site with a long axis \>1.0cm (according to the Lugano2014 criteria). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

• CD19 positive (detected by immunohistochemistry \[IHC\]).

• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for hematological toxicities and clinically non-significant toxicities such as alopecia).

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

• Absolute neutrophil count (ANC) ≥ 1 x 10\^9/L, Platelet count ≥50 x 10\^9/ L, hemoglobin (Hgb) ≥ 80g/L (hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions above).

• Adequate renal, hepatic, pulmonary and cardiac function defined as:

‣ 1 Serum creatinine≤1.5 upper limit of normal (ULN) or creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min.

‣ 2 Serum alanine aminotransferase / aspartate aminotransferase (ALT/ AST) ≤ 3 upper limit of normal (ULN); Total bilirubin ≤ 1.5 ULN, except in subjects with 3) Gilbert's syndrome.

‣ 3 Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.

‣ 4 Coagulation Function: International Normalized Ratio (INR) ≤ 1.5 times the upper limit of normal (ULN), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 times ULN.

‣ 5 Baseline oxygen saturation \>91% on room air.

⁃ Subjects of both genders who are willing to practice birth control from the time of consent through 6 months after the completion of conditioning chemotherapy. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).

⁃ Voluntarily participate in this clinical trial and sign an informed consent form.

Locations
Other Locations
China
Biotherapeutic Department of Chinsese PLA Gereral Hospital
RECRUITING
Beijing
Contact Information
Primary
Weidong Han, Ph.D
hanwdrsw@sina.com
010-66937231
Backup
Yang Liu, M.D
liuyang301blood@163.com
010-66939460
Time Frame
Start Date: 2025-06-20
Estimated Completion Date: 2027-05-31
Participants
Target number of participants: 30
Treatments
Experimental: CAR19TIF cells
Patients with r/r B Cell Lymphoma conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CAR19TIF cells.
Related Therapeutic Areas
Sponsors
Leads: Chinese PLA General Hospital

This content was sourced from clinicaltrials.gov

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