Relmacabtagene Autoleucel Combined With Sintilimab for Relapsed/Refractory B-cell Lymphoma

A Single-arm, Phase II Clinical Study of Relmacabtagene Autoleucel Combined With Sintilimab for Relapsed/Refractory B-cell Lymphoma.

This is a prospective, single-arm, multicenter, phase II clinical trial to evaluate the efficacy and safety of Relmacabtagene Autoleucel in combination with the Sintilimab regimen for the treatment of relapsed/refractory B-cell lymphoma

Relmacabtagene Autoleucel treatment: Patients will receive intravenous fludarabine (25 mg/m²/day for 3 days) and cyclophosphamide (250 mg/m²/day for 3 days) for lymphodepletion, with adjustments based on hematologic and renal function.Relmacabtagene Autoleucel will be reinfused 2 to 7 days after lymphodepletion.

Sintilimab treatment: Patients will receive intravenous Sintilimab (200 mg every 3 weeks) starting on Day 28 after reinfusion, continuing until disease progression or intolerable toxicity, with a maximum duration of 1 year.

Primary endpoint: The complete response rate (CRR) at 3 months.

Inclusion Criteria:

1. The patient must be aware of and voluntarily sign the informed consent form (ICF).
2. Aged between 18 and 70 years, both male and female.
3. Pathologically diagnosed with DLBCL, FL, or MCL, with histological confirmation of CD19 positivity (immunohistochemistry or flow cytometry, with flow cytometry used for re-evaluation if immunohistochemistry is CD19-negative).
4. The patient must be willing to receive regorafenib and sintilimab treatment and be deemed suitable for this treatment by the investigator.
5. Relapsed/refractory DLBCL, FL, or MCL.
6. At least one measurable or evaluable lesion.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
8. Expected survival of ≥3 months.
9. Adequate function of the heart, lungs, liver, kidneys, and other organs.

Exclusion Criteria:

1. History of another malignancy that has not been in complete remission for at least 2 years, except for: non-melanoma skin cancer, completely resected stage I tumors with low recurrence potential, treated localized prostate cancer, biopsy-confirmed cervical carcinoma in situ, or squamous intraepithelial lesions detected by Pap smear and so on.
2. Active Hepatitis B: a) Positive for Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb) , with HBV-DNA below the lower limit of the reference value can be included.
3. Hepatitis C, HIV, or syphilis infection.
4. Uncontrolled systemic fungal, bacterial, viral, or other infections.
5. Acute or chronic graft-versus-host disease (GVHD).
6. Known hypersensitivity or allergy to any study drug or excipient.
7. Clinically significant central nervous system (CNS) disease or symptoms, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychiatric illness.
8. Pregnant or breastfeeding women, and women of childbearing age who do not wish to use contraception.
9. Mentally ill individuals or those unable to provide informed consent.
10. The investigator deems the patient unsuitable for the study due to medical, psychological, familial, social, or geographical reasons or an inability to comply with the study protocol.
11. Previous CAR-T cell therapy or other gene-modified T-cell treatments.
12. Previous CD19-targeted therapy.
13. Previous allogeneic hematopoietic stem cell transplantation.