Study of Targeted CD22/CD19 CAR-T Therapy for First-line Consolidation of B-cell Lymphoma

NCT07094477 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: S2025-124-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy and safety of targeted CD22/CD19 CAR-T cell immunotherapy for first-line consolidation therapy of high-risk invasive B-cell lymphoma.

Conditions

Lymphoma

Keywords

B-cell lymphoma

Outcome Measures

Primary Outcomes (1)

• 1-year progression free survival rate (1-year-PFS)

  The 1-year progression free survival rate (1-year-PFS) of targeted CD22/CD19 CAR-T cell immunotherapy for first-line consolidation therapy of high-risk invasive B-cell lymphoma refers to the proportion of disease progression that occurs within one year after treatment in patients.

  1 year after treatment

Secondary Outcomes (7)

• overall survival (OS)

  1 year after treatment

• time to progression (TTP)

  1 year after treatment

• disease free survival (DFS)

  1 year after treatment

• duration of response (DOR)

  1 year after treatment

• event free survival (EFS)

  1 year after treatment

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

patients with high-risk invasive B-cell lymphoma who accept targeted CD22/CD19 CAR-T cell immunotherapy for first-line consolidation therapy

Drug: CD22/CD19 CAR-T cell immunotherapy

Interventions

CD22/CD19 CAR-T cell immunotherapy DRUG

targeted CD22/CD19 CAR-T cell immunotherapy

Also known as: CAR-T cell immunotherapy

Assigned Interventions

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. With the patient's consent and signed informed consent form, willing and able to comply with the planned visits, research treatments, laboratory tests, and other experimental procedures; 2. CD19 and/or CD22 positive large B-cell lymphoma (LBCL) diagnosed by cytology or histology according to WHO 2016 standards, including diffuse large B-cell lymphoma (DLBCL), high-grade lymphoma (HGBL), etc.: 1) The patient's disease is still evaluated as partial response (PR) after induction treatment with standard first-line chemotherapy regimen, or 2) The patient's disease reaches complete response (CR) after induction treatment with standard first-line chemotherapy regimen, but there are high-risk factors at the time of onset; 3. The possible high-risk factors for the patient's onset of the disease are as follows: 1) FISH confirmed high-grade B-cell lymphoma with double or triple strikes, accompanied by MYC and BCL2 and/or BCL6 rearrangements; 2) Advanced B-cell lymphoma with 11q abnormalities/Burkitt like lymphoma with 11q abnormalities; 3) The International Prognostic Index (IPI) at the time of initial diagnosis is 2-5 points; The Age Adjusted International Prognostic Index (aaIPI) is 2-3 points; The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score ranges from 4-8 points in the United States; 4) Immunohistochemical CD5 positivity; 5) Immunohistochemistry suggests dual expression of MYC and BCL-2 (recommended dual expression threshold is MYC ≥ 40%, BCL2 ≥ 50%); 6) Gene sequencing shows TP53 mutation; 7) The second-generation sequencing (NGS) suggests molecular typing as MCD subtype and N1 subtype; 4. Age range from 18 to 85 years old, male or female; 5. Subjects with physical fitness status scores ranging from 0 to 2 in the Eastern Cooperative Oncology Group (ECOG) in the United States; 6. Expected survival period from the date of signing the informed consent form is greater than 3 months; 7. HGB ≥ 60g/L; 8. The absolute value of neutrophils in peripheral blood is ≥ 1000/μl, and the platelet count is ≥ 45000/μl; 9. Liver and kidney function, as well as heart and lung function, meet the following requirements: 1) Total bilirubin (TBIL) ≤ 1.5 times the upper limits of normal (ULN), except for subjects with Gilbert's syndrome; 2) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN; 3) Serum Creatinine (Cr) ≤ 1.5 times ULN or Creatinine Clearance Rate (CCr) ≥ 60mL/min, estimated based on the Cockcroft Gault formula; 4) The left ventricular ejection fraction (LVEF) of the heart is ≥ 50%. Echocardiography (ECHO) confirms no pericardial effusion and no clinically significant arrhythmia; 5) Baseline transcutaneous oxygen saturation under indoor ventilation\>92%; 6) No clinically significant pleural effusion; 10. Participants with pregnancy plans must agree to take contraceptive measures for a continuous period of 6 months from before enrollment in the study until the end of the study; If the subject is pregnant or suspected of being pregnant, the researcher should be notified immediately.

You may not qualify if:

• \. Have received any form of chimeric antigen receptor cell therapy or other genetically modified T cell therapy; 2. Has a history of severe immediate hypersensitivity reactions to aminoglycoside antibiotics and other essential medications; 3. Known history of human immunodeficiency virus (HIV) infection or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics (active HBV infection is defined as: a. HBV DNA quantification ≥ 2000 IU/ml; b. ALT ≥ 2 times the normal upper limit value; c. Exclude hepatitis caused by the disease itself, medication, or other reasons; All three conditions must be met simultaneously. If a patient is diagnosed with active HBV infection at the time of initial diagnosis and becomes non active HBV infection after anti HBV treatment, they can be included in this study under the premise of sufficient anti HBV treatment; 4. Non hematological tumors (such as lymphoma) associated liver and kidney dysfunction: ALT\>3 times the upper limit of normal, AST\>3 times the upper limit of normal, TBIL\>2 times the upper limit of normal, serum creatinine clearance rate\<30 mL/min; 5. History of myocardial infarction, cardiac angioplasty or coronary stent implantation, unstable angina, active arrhythmia, or other clinically significant cardiovascular diseases within the 12 months prior to enrollment; 6. Other serious medical diseases may have an impact on this study (such as diabetes, gastric ulcer, other serious respiratory and circulatory diseases, severe autoimmune diseases or congenital immune defects, severe infection and inability to be effectively controlled), as well as other diseases with high risk of disease change; 7. Has a history of severe immediate hypersensitivity reactions to any medication necessary for use in this study; History of severe allergy to biological products (including antibiotics); 8. Female subjects who are currently pregnant or breastfeeding (with potential risks to the fetus or infant from pre-treatment chemotherapy regimens); 9. The researchers determined that the subjects were unable to complete all the required visit surveys or diagnostic procedures (including medium - and long-term follow-up visits) as per the study protocol, had poor willingness to participate in the study, were unwilling to join and fully comply with the study arrangements, and had insufficient compliance with the study by the subjects and their families. The decision-making power belongs to the researcher; 10. The subjects who have previously suffered from other malignant tumors cannot be included in this study unless they are disease-free and have not received any form of anti-tumor treatment for at least 3 years (except for skin tumors of non malignant melanoma and in situ cancers occurring in the cervix, bladder, breast, etc.); 11. History of receiving live vaccines within 6 weeks prior to initiating the pre-treatment plan; 12. Those who have undergone large-scale surgical treatment (excluding lymph node biopsy) within the past 14 days, or those who are expected to undergo large-scale surgical treatment during the treatment process; 13. There are other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the study results, as well as patients deemed unsuitable by the researchers to participate in this study.

Sponsors & Collaborators

• Daihong Liu: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Related Publications (7)

• Khan AN, Asija S, Pendhari J, Purwar R. CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for? Eur J Haematol. 2024 Jan;112(1):6-18. doi: 10.1111/ejh.14076. Epub 2023 Aug 7.

  PMID: 37545253 BACKGROUND

• Baker DJ, Arany Z, Baur JA, Epstein JA, June CH. CAR T therapy beyond cancer: the evolution of a living drug. Nature. 2023 Jul;619(7971):707-715. doi: 10.1038/s41586-023-06243-w. Epub 2023 Jul 26.

  PMID: 37495877 BACKGROUND

• CD19/CD22 Dual-Targeted CAR-T Therapy Active in Relapsed/Refractory DLBCL. Oncologist. 2020 Jul;25 Suppl 1(Suppl 1):S12-S13. doi: 10.1634/theoncologist.2020-0560. Epub 2020 Jun 26.

  PMID: 32589304 BACKGROUND

• Nguyen TT, Thanh Nhu N, Chen CL, Lin CF. Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis. Cancer Med. 2023 Sep;12(18):18767-18785. doi: 10.1002/cam4.6497. Epub 2023 Sep 5.

  PMID: 37667978 BACKGROUND

• Zeng C, Cheng J, Li T, Huang J, Li C, Jiang L, Wang J, Chen L, Mao X, Zhu L, Lou Y, Zhou J, Zhou X. Efficacy and toxicity for CD22/CD19 chimeric antigen receptor T-cell therapy in patients with relapsed/refractory aggressive B-cell lymphoma involving the gastrointestinal tract. Cytotherapy. 2020 Mar;22(3):166-171. doi: 10.1016/j.jcyt.2020.01.008. Epub 2020 Feb 13.

  PMID: 32063474 BACKGROUND

• Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M, Younes S, Natkunam Y, Ozawa MG, Yang E, Tamaresis J, Chinnasamy H, Ehlinger Z, Reynolds W, Lynn R, Rotiroti MC, Gkitsas N, Arai S, Johnston L, Lowsky R, Majzner RG, Meyer E, Negrin RS, Rezvani AR, Sidana S, Shizuru J, Weng WK, Mullins C, Jacob A, Kirsch I, Bazzano M, Zhou J, Mackay S, Bornheimer SJ, Schultz L, Ramakrishna S, Davis KL, Kong KA, Shah NN, Qin H, Fry T, Feldman S, Mackall CL, Miklos DB. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021 Aug;27(8):1419-1431. doi: 10.1038/s41591-021-01436-0. Epub 2021 Jul 26.

  PMID: 34312556 BACKGROUND

• Wei G, Zhang Y, Zhao H, Wang Y, Liu Y, Liang B, Wang X, Xu H, Cui J, Wu W, Zhao K, Nagler A, Chang AH, Hu Y, Huang H. CD19/CD22 Dual-Targeted CAR T-cell Therapy for Relapsed/Refractory Aggressive B-cell Lymphoma: A Safety and Efficacy Study. Cancer Immunol Res. 2021 Sep;9(9):1061-1070. doi: 10.1158/2326-6066.CIR-20-0675. Epub 2021 Jul 21.

  PMID: 34290048 BACKGROUND

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Dai-Hong Liu, Dr.

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Model Details: Prospective Assignment

Study Record Dates

• First Submitted: June 1, 2025
• First Posted: July 30, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)