## Protocol Section
### Identification Module
**NCT ID:** NCT06427213

**Brief Title:** This is a Phase II, Open-label, Multicentre Study of Zanubrutinib-containing Regimens in Patients With Newly Diagnosed Mantle Cell Lymphoma

**Official Title:** A Study of the Zanubrutinib-containing Regimens in Patients With Newly Diagnosed Mantle Cell Lymphoma

#### Organization Study ID Info
**ID:** IIT-TN MCL
#### Organization
**Class:** OTHER_GOV
**Full Name:** Henan Cancer Hospital
### Status Module
#### Completion Date
**Date:** 2029-12-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-19

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-12-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-20

**Type:** ESTIMATED

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-19
**Study First Submit QC Date:** 2024-05-19
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER_GOV

**Name:** Henan Cancer Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** This is a phase II, open-label, multicentre study of Zanubrutinib-containing regimens in patients with newly diagnosed mantle cell lymphoma.

**Detailed Description:** This study is a prospective, multicenter, investigator-initiated clinical trial to evaluate the efficacy and safety of zanubrutinib-containing regimens in the treatment of newly diagnosed elderly or young patients with high risk MCL, aiming to find a more optimal treatment regimen for elderly or young patients with high risk MCL to improve the efficacy, survival time and quality of life of patients.

In elderly patients arm：patients start with the induction therapy of zanubrutinib combined with obinutuzumab for 1 year and then entered the maintenance therapy of zanubrutinib orally until intolerable toxicity or disease progression

In young patients with high risk arm：patiens \<65 years，and meet one or more of the following risk factors: TP53 mutation, blastoid/pleomorphic type, high sMIPI score. patients start with 6 cycles of induction therapy with zanubrutinib combined with R-BAC regimen, and the patients who achieve CR/PR and meet the transplantation criteria will receive ASCT consolidationand, then received maintenance therapy with zanubrutinib. otherwise, Patients who is ineligible for transplantation，will take zanubrutinib orally until intolerable toxicity or disease progression.

### Conditions Module

**Conditions:**

- Lymphoma, Mantle-Cell

- Lymphoma, Non-Hodgkin

**Keywords:**

- Zanubrutinib

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 41

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Induction: Zanubrutinib and Obinutuzumab 1year

Maintenance: Zanubrutinib continued until progression

**Intervention Names:**

- Drug: Zanubrutinib,Obinutuzumab

**Label:** Elder Patients（≥65）

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Induction: Zanubrutinib and R-BAC 6 cycles

Consolidation: ASCT（If eligible for transplantation），Otherwise, the patient was directly entered into maintenance treatment

Maintenance: Zanubrutinib continued until progression

**Intervention Names:**

- Drug: Zanubrutinib and R-BAC

**Label:** Young Patients with High risk （≥18，<65）

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Elder Patients（≥65）

**Description:** Zanubrutinib, 160mg PO BID. C1D17 continuously for 1 year or until progressive disease； Obinutuzumab ：Obinutuzumab will be administered 1,000 mg intravenously on days 1, 8, and 15 of cycle 1, then 1,000 mg on day 1 of cycles 2 to 6, then 1,000 mg every 8 weeks，up to 20 doses. 1 cycle = 28 days.

Maintenance: Zanubrutinib, 160mg PO BID

**Name:** Zanubrutinib,Obinutuzumab

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Young Patients with High risk （≥18，<65）

**Description:** Induction: Zanubrutinib and R-BAC 6 cycles

Consolidation: ASCT（If eligible for transplantation），Otherwise, the patient was directly entered into maintenance treatment

Maintenance: Zanubrutinib continued until progression

**Name:** Zanubrutinib and R-BAC

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.

**Measure:** Objective Response rate after induction

**Time Frame:** 3 yeas

#### Secondary Outcomes

**Description:** Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.

**Measure:** Complete remission rate after Interim treatment

**Time Frame:** 3 years

**Description:** MRD negativity rate after induction treatment

**Measure:** MRD negativity rate after induction

**Time Frame:** 3 years

**Description:** The time from start of treatment to progression or death from any cause

**Measure:** Progression free survival (PFS)

**Time Frame:** 5 years

**Description:** The time from start of treatment to death from any cause

**Measure:** Overall survival (OS)

**Time Frame:** 5 years

**Description:** Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0

**Measure:** Percentage of Participants With Adverse Events

**Time Frame:** 5 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Voluntary participation in clinical study; Fully understand and understand the study and sign the informed consent form (ICF);Willingness to follow and ability to complete all study steps
2. Histopathologically confirmed mantle cell lymphoma according to the 5th edition of the World Health Organization (WHO)，previous untreatment for mantle-cell lymphoma (MCL)
3. The elderly group ≥65 years old;The young group was ≥18 years old and \< 65 years old.
4. ECOG Performance Status 0-3
5. Life expectancy of at least 3 months
6. At least one evaluable lesion according to 2014 Lugano criteria;
7. Proper functioning of the major organs, no major heart, lung, liver, kidney, or immunodeficiency (no blood transfusion, granulocyte colony-stimulating factor, or other medical support within 7 days before starting the study) :Hemoglobin (HB)≥60 g/L;Absolute neutrophil count(ANC)≥0.5×10\^9/L;Platelet count（PLT）≥50×10\^9/L;AST and ALT ≤ 2.5 x ULN；Total bilirubin ≤ 1.5 times the ULN;Ccr≥40ml/min（Cockcroft-Gault ）；Left Ventricular Ejection Fraction (LVEF) ≥ 50%

Exclusion Criteria:

1. The presence of other tumors could affect the study medication or interfere with the results;
2. Patients require treatment with strong or moderate CYP3A inhibitors;
3. Pregnant or lactating women;
4. Known to be allergic to the test drug ingredients;
5. Subjects of childbearing potential who are unwilling to use highly effective contraceptive methods;
6. Live vaccination was administered within 28 days prior to treatment
7. Known human immunodeficiency virus (HIV) infection or suggested active B or C infection The following serologic status of hepatitis C virus infection: 1) Hepatitis B virus (HBV) DNA positive. Positive hepatitis B surface antigen (HBsAg) or anti-hepatitis B core antibody (HBcAb) seropositive if HBV DNA is undetectable and willing to accept Monthly surveillance for HBV reactivation was eligible. 2) Hepatitis C virus (HCV) antibody positive. For patients with HCV antibodies present, if undetectable HCV RNA, can be included;
8. Severe coagulopathy and serious impairment of heart, brain, lung, liver, kidney and other organs
9. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months;
10. Any risk that is considered by the investigator to be likely to affect the safety of the subjects or to pose a risk to the study And vital diseases, medical conditions, or organ system insufficiency.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** drzhouks77@163.com

**Name:** keshu Zhou

**Phone:** 0371-65587306

**Role:** CONTACT

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: M11222

- Name: Lymphoma, Non-Hodgkin

- Relevance: HIGH

- As Found: Lymphoma, Non-Hodgkin

- ID: M22307

- Name: Lymphoma, Mantle-Cell

- Relevance: HIGH

- As Found: Lymphoma, Mantle-Cell

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma

- ID: T3601

- Name: Mantle Cell Lymphoma

- Relevance: HIGH

- As Found: Mantle Cell Lymphoma

### Condition Browse Module - Meshes

- ID: D000008223

- Term: Lymphoma

- ID: D000020522

- Term: Lymphoma, Mantle-Cell

- ID: D000008228

- Term: Lymphoma, Non-Hodgkin

### Intervention Browse Module - Ancestors

- ID: D000074322

- Term: Antineoplastic Agents, Immunological

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000092004

- Term: Tyrosine Kinase Inhibitors

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M288906

- Name: Obinutuzumab

- Relevance: HIGH

- As Found: Contraction

- ID: M42199

- Name: Zanubrutinib

- Relevance: HIGH

- As Found: Allowing

- ID: M1346

- Name: Antineoplastic Agents, Immunological

- Relevance: LOW

- As Found: Unknown

- ID: M2889

- Name: Tyrosine Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T22

- Name: Tyrosine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000543332

- Term: Obinutuzumab

- ID: C000629551

- Term: Zanubrutinib

### Misc Info Module

- Version Holder: 2024-05-31
