This is a single-arm, multi-center, prospective, phase II study. The primary objective is to assess the efficacy and safety of bendamustine/orelabrutinib combined with an anti-CD20 monoclonal antibody in treatment-naïve patients with mantle cell lymphoma.
Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma and is considered to be incurable. MCL patients have varied clinical presentations (generally symptomatic to an asymptomatic indolent clinical course). Over the past decade, significant advances in the treatment of MCL have been achieved through intensive immunochemotherapy regimens and clinical trials evaluating novel targeted agents and combination strategies. However, early disease relapse remains a frequent clinical challenge. Recently, combination regimens involving chemotherapy and targeted therapy have demonstrated promising efficacy with acceptable safety profiles. Bendamustine is a unique cytotoxic agent that induces apoptosis through activation of DNA damage stress responses, disruption of mitotic checkpoints, and induction of mitotic catastrophe. Zuberitamab is a novel anti-CD20 monoclonal antibody that demonstrates enhanced antibody-dependent cellular cytotoxicity compared with rituximab. Orelabrutinib is a potent, irreversible, and highly selective Bruton tyrosine kinase inhibitor. This study is a multicenter, prospective trial involving previously untreated patients with MCL. During the induction phase (cycles 1-4), all patients will receive bendamustine at a dose of 90 mg/m² in combination with anti-CD20 monoclonal antibody at 375 mg/m². After cycle 4, patients who achieve a complete response (CR) and are minimal residual disease (MRD) negative will continue to receive the same regimen (bendamustine 90 mg/m² plus anti-CD20 monoclonal antibody 375mg/m²) for cycles 5 to 6. In contrast, patients who are MRD positive will switch to a treatment regimen consisting of orelabrutinib at 150 mg combined with anti-CD20 monoclonal antibody at 375 mg/m². During the maintenance phase (cycles 7-24), patients who achieve CR and are MRD negative at cycle 4 will continue receiving bendamustine plus anti-CD20 monoclonal antibody, while MRD-positive patients will continue treatment with orelabrutinib plus anti-CD20 monoclonal antibody until disease progression, relapse, intolerable toxicities, death, loss to follow-up, or withdrawal of consent, whichever occurs first, with a maximum of 24 cycles.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Induction phase (cycle 1-6): Bendamustine (90 mg/m², day 1-2) +anti-CD20 monoclonal antibody (375 mg/m², day 0) from cycles 1-4. Patients who achieve CR and MRD negative continue to receive bendamustine (90 mg/m², day 1-2) + anti-CD20 monoclonal antibody (375 mg/m², day 0) from cycles 5-6; MRD positive patients receive orelabrutinib (150 mg) + anti-CD20 monoclonal antibody (375 mg/m², day 0). Maintenance phase (cycle 7-24): Patients who achieve CR and are MRD negative at cycle 4 receive bendamustine (90 mg/m², day 1-2) + anti-CD20 monoclonal antibody (375 mg/m², day 0); MRD-positive patients receive orelabrutinib (150 mg) + anti-CD20 monoclonal antibody (375 mg/m², day 0).
Fujian Provincial Cancer Hospital
Fuzhou, Fujian, China
Hebei Medical University Tumor Hospital
Shijiazhuang, Hebei, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
Shandong Cancer Hospital
Jinan, Shandong, China
Progression-free survival (PFS)
PFS is defined as the time from the initiation of treatment to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. Patients who remain alive and progression-free at the data cutoff date, PFS will be censored at the last tumor assessment date.
Time frame: From the date of the initiation of treatment until the date of first documented progression, up to 2 years.
Overall response rate (ORR)
The ORR is defined as the proportion of patients with a response of CR or PR.
Time frame: From the initiation of treatment to the end of therapy, up to 2 years.
Complete response rate (CRR)
Complete response rate is defined as the proportion of patients with a response of CR.
Time frame: From the initiation of treatment to the end of therapy, up to 2 years.
Duration of Response (DOR)
DOR is defined as the time from documentation of response to treatment to the first documentation of tumor progression or death due to any cause, whichever comes first.
Time frame: From the first demonstration of response until disease progression/death, up to 2 years.
Time to response (TTR)
TTR is defined as the time from the start of therapy to the first response.
Time frame: From the start of therapy to the first documentation of response.
Overall survival (OS)
OS is defined as the time from the initiation of treatment to death from any cause. Patients alive at the data cutoff date will have their OS censored at the date of the last follow-up.
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Tianjin Medical University Cancer Institute and Hospital
Tianjin, China
Time frame: From the date of the initiation of treatment until the date of death, up to 3 years.
Adverse events (AEs)
AEs will be graded according to the NCI-CTCAE Version 5.0.
Time frame: From the date of enrollment until the date of death, up to 3 years.