Novel Allogenic CD19-targeting CAR-γδT Cell Therapy (QH103E) in r/r NHL

NCT ID: NCT06838832

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-27
• Study Completion Date: 2028-03-01

Brief Summary

CD19-CAR-γδT cell therapy is a cellular immunotherapy targeting CD19 to perform CAR modification on allogeneic γδT cells. A novel version of the CAR-γδT product by gene editing (QH103E) that has been validated for resistance to alloreactive T cell killing and enhancement of memory efficacy will be used in this study.

This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) will be enrolled in the study and receive QH103E product infusion. Phase 1 (n=9 to 12) is dose escalation part, and phase 2 (n=15 to 20) is expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of QH103E in patients with r/r B-cell NHL.

Detailed Description

Phase 1 (dose escalation) In phase 1, 9-12 subjects will be enrolled. Subjects will receive 3 doses of QH103E therapy (1× 10^6 cells/kg; 3× 10^6 cells/kg; 6 × 10^6 cells/kg) increases from low dose to high dose according to the "3 + 3" principle:

1. Three patients were enrolled in the lowest dose group.

2. Subsequent patients were enrolled according to the following rules:

1. If the incidence of dose limiting toxicity (DLT) was 0/3, 3 patients were enrolled in the next high-dose group.

2. If the incidence of DLT was 1/3, 3 patients were enrolled at the same dose; If the incidence of DLT was 1/3 + 0/3, 3 patients were enrolled in the next high-dose group. If the incidence of DLT was 1/3 + 1/3, this dose was defined as maximum tolerated dose (MTD); If the incidence of DLT was 1/3 + 2/3 or 1/3 + 3/3, the previous dose was MTD.

3. If the incidence of DLT was 2/3 or 3/3, the previous dose was MTD. To ensure the safety of the subjects, the first subject in each dose group was observed for at least 28 days after the cell infusion. If no DLT occurred, the remaining two subjects could be enrolled and treated at the same dose level. The safety data of all subjects in each dose group until day 28 should be reviewed and tolerated before proceeding to the next dose group trial. No dose escalation was allowed for the same subject during the trial. If a subject drop out during the observation period due to non-DLT reasons, new subjects should be enrolled to make up for the number of subjects who drop out. Phase 2 (expansion cohort) In phase 2, 15 to 20 subjects will be enrolled and receive QH103E infusion at dose of RP2D, which will be determined based on the MTD, occurrence of DLT, the obtained efficacy results, pharmacokinetics/ pharmacodynamics and other data according to the phase 1.

Conditions

Non-hodgkin Lymphoma,B Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with refractory or relapsed B-cell NHL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, QH103E product.

Group Type: EXPERIMENTAL

Allogenic CD19-CAR-γδT cell

Intervention Type: BIOLOGICAL

Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (6× 10\^6 cells/kg); Phase 2 : dose of RP2D.

Fludarabine

Intervention Type: DRUG

Intravenous fludarabine 30~50 mg/m^2/day on days

-5, -4, and -3.

Cyclophosphamide

Intervention Type: DRUG

Intravenous cyclophosphamide 500\~1000 mg/m\^2/ day on days -5, -4, and -3.

Interventions

Allogenic CD19-CAR-γδT cell

Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (6× 10\^6 cells/kg); Phase 2 : dose of RP2D.

Intervention Type: BIOLOGICAL

Fludarabine

Intravenous fludarabine 30~50 mg/m^2/day on days

-5, -4, and -3.

Intervention Type: DRUG

Cyclophosphamide

Intravenous cyclophosphamide 500\~1000 mg/m\^2/ day on days -5, -4, and -3.

Intervention Type: DRUG

Other Intervention Names

Fludarabine Phosphate for Injection; Cyclophosphamide for Injection

Eligibility Criteria

Inclusion Criteria

1. Age 18-75 (inclusive).

2. Patients with histologically confirmed CD19-positive B-cell NHL.

3. Relapse after treatment with ≥2 lines systemic therapy for all the B-cell NHL disease types, or refractory disease for aggressive types (DLBCL-NOS, PMBCL, TFL and HGBCL). Relapse disease is defined as disease progression after last regimen. Refractory disease is defined as no CR to first-line therapy:

• PD as best response to first-line therapy, 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. The estimated survival time is over 3 months.

5. The Eastern Cooperative Oncology Group (ECOG) score is 0-2.

6. According to Lugano response criteria 2014, there should be at least one evaluable tumor focus. Evaluable tumor focus was defined as that with the longest diameter of intranodal focus > 1.5cm, the longest diameter of extranodal focus > 1.0cm assessed by computed tomography (CT) or magnetic resonance imaging (MRI).

7. Subjects must be willing to undergo either excised or large-needle lymph node or tissue biopsy, or provide formalin-fixed paraffin-embedded (FFPE) tumor tissue block or freshly cut unstained slides.

8. Functions of important organs meet the following requirements:

Echocardiography showed left ventricular ejection fraction ≥50%. Serum creatinine ≤1.5 × upper limit of normal range (ULN) or endogenous creatinine clearance ≥45mL/min (cockcroft-gault formula); Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤3 times ULN, Total bilirubin ≤1.5× ULN; Pulmonary function: ≤CTCAE grade1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment.

9. Blood routine (normal values shall not be obtained with growth factors, and hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions below): hemoglobin (Hgb) ≥80g/L, neutrophil count≥1×10^9/L, platelet (PLT) ≥75×10^9/L.

10. Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year.

Exclusion Criteria

12. No obvious hereditary diseases.

13. Able to understand the requirements and matters of the trial, and willing to participate in clinical research as required.

14. Informed consent must be signed.

1. During the screening period, there was central nervous system (CNS) invasion or a history of clinically significant central nervous system diseases, such as epilepsy and cerebrovascular diseases.

2. Women who are pregnant or breastfeeding, or who do not agree to use effective contraception during treatment and during the subsequent 1 year.

3. History of allogeneic hematopoietic stem cell transplantation, or organ transplantation.

4. History of other malignancies that have not been in remission.

5. Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy.

6. Received radiotherapy within 3 months before enrollment.

7. Received immunotherapy drugs within 4 weeks before enrollment, such as anti-programmed death 1 (PD-1) antibody, anti-programmed death ligand 1 (PD-L1) antibody, CD19/CD3-bispecific antibody, and so on.

8. Patients who received any immunocellular therapy within 6 months before enrollment.

9. Confirmed evidence showing positiveness of anti-CD19 scFv reaction in patient serum.

10. Patients who participated in other clinical trials within 4 weeks prior to enrollment.

11. Uncontrolled infectious diseases or other serious illnesses, including but not limited to infections [e.g., human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B (HBV) or C (HCV) infection], congestive heart failure, unstable angina, arrhythmias, or that pose an unpredictable risk in the opinion of the attending physician.

12. The presence of uncontrollable serous membrane fluid, such as massive pleural effusion or ascites.

13. A history of stroke or intracranial hemorrhage within 3 months prior to enrollment.

14. Major surgery or trauma occurred within 28 days prior to enrollment, or major side effects have not been recovered.

15. Received allogeneic cell therapy within 6 weeks prior to enrollment, such as donor lymphocyte infusion.

16. History of allergies to any of the ingredients in cell products.

17. Conditions in which a known mental or physical illness interferes with cooperation with the requirements of the study or disrupts the results or interpretation of the results and, in the opinion of the therapeutic investigator, makes the patient unfit for study participation.

18. There is the situation that the researcher's judgment will interfere with the whole study participation; Situations where there is significant risk to the subject; Or interferes with the interpretation of research data.

19. Inability to understand or unwillingness to sign informed consent.

20. Researchers believe that other reasons are not suitable for clinical trials.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Han weidong

Director of Biotherapeutic Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Biotherapeutic Department of Chinsese PLA Gereral Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Weidong Han

Role: CONTACT

hanwdrsw@sina.com

+86-010-55499341

Facility Contacts

Weidong Han, PH.D

Role: primary

hanwdrsw69@yahoo.com

010-66937463 ext. +86

Yang Liu, M.D

Role: backup

liuyang301blood@163.com

010-66939460 ext. +86

Other Identifiers

CHN-PLAGH-BT-091

Identifier Type: -

Identifier Source: org_study_id