Relapsed or Refractory B-cell Lymphoma
Conditions
Brief summary
This is a single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of pirtobrutinib as maintenance therapy in patients with relapsed or refractory B-cell lymphoma after commercial anti-CD19 CAR-T cell therapy.
Interventions
DRUGPirtobrutinib
Pirtobrutinib will be administered orally at a dose of 200 mg once daily for 6 months, beginning on Day 30 after commercial anti-CD19 CAR-T cell infusion. Dose interruption, dose reduction, or treatment discontinuation will be performed according to protocol-specified toxicity management rules.
BIOLOGICALSecond Infusion of Commercial Anti-CD19 CAR-T Cells
A second infusion of commercial anti-CD19 CAR-T cells may be administered after completion of 6 months of pirtobrutinib maintenance therapy in selected patients who do not achieve complete response, or who achieve complete response but remain ctDNA-positive, based on investigator assessment and protocol-defined criteria.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to understand and voluntarily sign the informed consent form. * Age 18 years or older, male or female. * Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, or transformed follicular lymphoma (tFL). * Eastern Cooperative Oncology Group performance status of 0 to 2. * Has received commercial anti-CD19 CAR-T cell therapy, with informed consent obtained before Day 28 after CAR-T cell infusion. * Prior anti-lymphoma therapy-related adverse events, especially CAR-T-related adverse events, have stabilized and recovered to Grade 1 or lower, except for clinically insignificant toxicities.
Exclusion criteria
* History of other malignancies, except non-melanoma skin cancer without recurrence for more than 3 years, carcinoma in situ, such as cervical, bladder, or breast carcinoma, or follicular lymphoma. * Prior autologous or allogeneic hematopoietic stem cell transplantation. * Active or suspected uncontrolled fungal, bacterial, viral, or other infection requiring intravenous treatment. Patients with uncomplicated urinary tract infection or uncomplicated bacterial pharyngitis may be enrolled if responding to active treatment. * History of immunodeficiency, including human immunodeficiency virus infection; positive treponema pallidum antibody; active hepatitis B virus infection; or active hepatitis C virus infection. * Current or prior history of benign central nervous system disease, such as seizure, cerebrovascular ischemia or hemorrhage, dementia, cerebellar disease, or any central nervous system-related autoimmune disease. * Lymphoma involvement of the atrium or ventricle. * Autoimmune disease requiring systemic immunosuppressive or immunomodulatory therapy within 2 years. * History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment. * Any comorbidity that may affect or interfere with safety or efficacy assessment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | At 6 months after initiation of pirtobrutinib maintenance therapy | CRR is defined as the proportion of patients who achieve complete response according to the Lugano 2014 criteria at 6 months after initiation of pirtobrutinib maintenance therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best complete response rate (bCRR) | Up to 24 months | bCRR is defined as the proportion of patients whose best response is complete response according to the Lugano 2014 criteria. |
| Best objective response rate (bORR) | Up to 24 months | bORR is defined as the proportion of patients whose best response is complete response or partial response according to the Lugano 2014 criteria. |
| Objective response rate (ORR) | At 6 months after initiation of pirtobrutinib maintenance therapy | ORR is defined as the proportion of patients who achieve complete response or partial response according to the Lugano 2014 criteria at 6 months after initiation of pirtobrutinib maintenance therapy. |
| Duration of complete response (DoCR) | Up to 24 months | DoCR is defined as the time from the first documented complete response to disease progression or death from any cause, whichever occurs first. |
| Duration of response (DOR) | Up to 24 months | DOR is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first. |
| Progression-free survival (PFS) | Up to 24 months | PFS is defined as the time from enrollment to disease progression or death from any cause, whichever occurs first. |
| Overall survival (OS) | Up to 24 months | OS is defined as the time from enrollment to death from any cause. |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | Up to 30 days after the last dose of pirtobrutinib | The incidence and severity of adverse events will be assessed and graded according to the National Cancer In Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
Countries
China
Outcome results
None listed