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

Untreated Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05504603
• Other study ID #: Jinzm 004
• Status: Recruiting
• Phase: Phase 2
• Start date: July 27, 2020
• Est. completion date: July 26, 2025

Study information

• Verified date: August 2022
• Source: The First Affiliated Hospital of Soochow University
• Contact: Zhengming Jin
• Phone: +86 0512 67781856
• Email: jinzhengming519519[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 Patients who are evaluated as SD and PD will be withdrawn from the trial,while those who achieve PR and CR will be further stratified according to their age and physical status.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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: July 26, 2025
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Untreated Mantle Cell Lymphoma

Intervention

Drug:
• zanubrutinib and rituximab
zanubrutinib 160mg PO BID d1-28; rituximab 375mg/m2 IVGTT d1,8,15,22. Other name: Part A
• zanubrutinib and rituximab
zanubrutinib 160mg PO BID d1-28; rituximab 375mg/m2 IVGTT d1. Other name: Part B
• BEAM pretreatment
semustine 250mg/m2 PO d1; etoposide 200mg/m2 IV d2-5; cytarabine 400mg/m2 IV d2-5; melphalan 140mg/m2 IV d6.
• zanubrutinib maintenance
zanubrutinib 160mg PO BID.

Locations

Country	Name	City	State
China	the First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate(ORR) in all patients	The rate of patients who achieved complete response and partial response after ZR combined immunotherapy	At the end of cycle 3 and cycle 5(each cycle is 28 days)
Primary	Complete Response Rate(CRR) in all patients	The rate of patients who achieved complete response after ZR combined immunotherapy.	At the end of cycle 3 and cycle 5(each cycle is 28 days)
Primary	Overall Response Rate(ORR) in patients received ASCT	The rate of patients who achieved complete response and partial response after ASCT.	1 month after ASCT
Primary	Complete Response Rate(CRR) in patients received ASCT	The rate of patients who achieved complete response after ASCT.	1 month after ASCT
Secondary	Overall Survival (OS)	OS will be assessed from the first ZR given to date of death or end of follow-up.	up to 24 months after the last patient's enrollment.
Secondary	Progression Free Survival (PFS)	PFS will be assessed from the first ZR given to date of progression, relapse, death or end of follow-up.	up to 24 months after the last patient's enrollment.
Secondary	Incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events	The safety and tolerability of the therapeutic regimen measured by the incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events.	initiation of study drug until 30 days after last dose.
Secondary	Minimal Residual Disease (MRD)		At the end of cycle 5 ZR (each cycle is 28 days) and 1 month after ASCT.