Zanubrutinib-rituximab(ZR) in Patients With Newly Diagnosed Untreated Mantle Cell Lymphoma

A Phase 2 Study of Zanubrutinib-rituximab(ZR) in Patients With Newly Diagnosed Untreated Mantle Cell Lymphoma

The proposed study is a prospective, single-center, single-arm and open-ended phase II study in patients over the age of 18 with previously untreated mantle cell lymphoma(MCL). The primary objective of this study is to explore the safety and efficacy of a new chemo-free treatment pattern zanubrutinib-rituximab(ZR) in newly diagnosed MCL.

The study will start with an initial 28-days of induction immunotherapy with ZR and 4 cycles of consolidation immunotherapy with ZR，following imaging examinations to evaluate response rates. Patients who are evaluated as SD and PD will be withdrawn from the trial,while those who achieve PR and CR will be further stratified according to their age and physical status. The older or frail patients who are ineligible for ASCT will take zanubrutinib orally until intolerable toxicity or disease progression. Patients who are young and fit for transplantation will receive ASCT consolidation. After ASCT, patients with CR will end therapy and enter the follow-up stage, while patients with PR will continue to take zanubrutinib orally until intolerable toxicity or disease progression.

Inclusion Criteria:

1. Histopathologically or Cytologically confirmed Mantle Cell Lymphoma(excluding indolent Mantle Cell Lymphoma) by the 2008 World Health Organization (WHO) Classification of diseases;
2. Initial untreated patients;
3. Age ≥ 18 years;
4. ECOG score 0-2;
5. Women must not be pregnant or breastfeeding and agree to avoid pregnancy prior to study entry, for the duration of study participation, and for 12 months thereafter. Male patients must agree that their spouses will not become pregnant during the study period and for 12 months thereafter;
6. Patients must have measurable disease (i.e., ≥ 1.0 cm in lymph nodes diameter; or skin lesions assessed by physical examination);
7. Written informed consent obtained from the subject.

Exclusion Criteria:

1. Indolent Mantle Cell Lymphoma;
2. Patients with severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal)
3. Uncontrolled active infection, with the exception of tumor-related B symptom fever;
4. Patients with organic heart disease with clinical symptoms or cardiac dysfunction (NYHA grade ≥2);
5. Co-existence of other tumors;
6. Any other psychological conditions that prevent patients from participating in the study or signing the informed consent form.