A Single-arm, Single-center, Open-label Phase II Study of Zanubrutinib Combined With R-CHOP/R-DHAP in Newly Diagnosed Mantle CellLymphoma Patients

NCT06255704 | Not Yet Recruiting Phase 2

• 1 other identifier: MCL BTKi immunochemotherapy
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation the efficacy and safety of Zanubrutinib + R-CHOP/R-DHAP for the treatment mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• CR rate after 6 cycles of induction therapy

  To evaluate the CR rate after Zanubrutinib-based induction therapy in subjects with newly diagnosed MCL.

  18 weeks

Secondary Outcomes (5)

• ORR rate after 6 cycles of induction therapy

  18 weeks

• Progression free survival (PFS)

  60 weeks

• Overall survival (OS)

  60 weeks

• duration of response, DOR

  60 weeks

• MRD negative rate at the end of induction therapy

  18 weeks

Study Arms (1)

Zanubrutinib and RCHOP/RDHAP

EXPERIMENTAL

Patients will receive zanubrutinib and RCHOP alternating with RDHAP for a total of 6 cycles of induction therapy, and patients who achieve complete response after 6 cycles of induction therapy will be eligible to enter a 2-year maintenance treatment period of zanubrutinib in combination with rituximab

Drug: Zanubrutinib and RCHOP/RDHAP

Interventions

Zanubrutinib and RCHOP/RDHAP DRUG

Alternating 3× R-CHOP/ 3× R-DHAOx, every 21 days plus oral Zanubrutinib in cycle 1, 3, 5 in combination with R-CHOP: R-CHOP (cycle 1,3,5): Rituximab 375 mg/m2 D1, I.V. Cyclophosphamide 750 mg/m2 D1, I.V. Doxorubicine 50 mg/m2 D1, I.V. Vincristine 1.4mg/m2(max 2mg)D1, I.V. Prednisone 100mg D1-5, oral Zanubrutinib 160mg BID D1-21, oral R-DHAP(cycle 2,4,6): Dexamethasone 40mg D1-4 oral/I.V. Rituximab 375mg/m2 D1, I.V. Ara-C 2×2g/m2 q12h D2, I.V. Cisplatin 100mg/m2 D1, I.V. Maintenance: Zanubrutinib, 160mg PO BID, rituximab 375mg/m2 repeated every 8 weeks, treatment will continue for up to 2 years or until progressive disease。

Zanubrutinib and RCHOP/RDHAP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of MCL according to WHO classification;
• Previously untreated MCL.
• Age ≥ 18 and ≤ 70 years old.
• ECOG, 0\~2.
• Suitable for high-dose treatment including high-dose Ara-C.
• Stage II-IV (Ann Arbor).
• Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI). Measurable disease was defined as at least 1 lymph node \> 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions; in case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations.
• The following laboratory tests during the screening period (unless related to MCL disease)
• \) Neutrophils ≥1×109/L within 7 days prior to study entry, and no growth factor support therapy.
• \) Platelets ≥75×109/L within 7 days prior to study entry without growth factor support or blood transfusion.
• \) Hemoglobin ≥75g/L shall not be transfused within 7 days before the test. If bone marrow is involved, neutrophils ≥0.75×109/L, platelets ≥50×109/L, hemoglobin ≥50g/L)
• \) Creatinine clearance ≥30ml/min
• \) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× upper limit of normal (ULN).
• International Standardized ratio (INR) ≤1.5 and activated partial prothrombin kinase time (APTT) ≤1.5×ULN. If there is a clotting factor inhibitor that causes an elevated INR or prolonged APTT, it is up to the investigator to decide whether to enroll the patient.
• Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug

You may not qualify if:

• Known CNS involvement of MCL, Leukemic non-lymphonodular mantle cell lymphoma was excluded.
• Major surgery within 4 weeks of screening
• Concomitant or previous malignancies within the last 2 years other than basal cell skin cancer or in situ uterine cervix cancer
• Clinically significant cardiovascular disease such as uncontrolled arrhythmias and hypertension , congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below 50%（AHA，2016）
• QTcF \> 450 msec or other significant electrocardiogram (ECG) abnormalities including second-degree atrioventricular block Type II, or third-degree atrioventricular block
• Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of zanubrutinib itself or to the excipients in its formulation)
• Requires treatment with strong CYP3A inhibitors or strong CYP3A inducers
• Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
• Active infection including infections requiring oral or intravenous antimicrobial therapy
• Patients with unresolved hepatitis B or C infection or known HIV positive infection
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
• Pregnancy or lactation
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk
• Participation in another clinical trial within 30 days before enrollment in this study
• poor compliance

Sponsors & Collaborators

• Shanxi Province Cancer Hospital: lead

Study Sites (1)

Hematology Department of ShanXi Cancer Hospital

Taiyuan, Shanxi, 030013, China

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Liping Su, M.D.

  Hematology Department of ShanXi Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liping Su, M.D.

CONTACT

13835158122; sulp2005@sohu.com

Zhiqiang Zhao, M.D.

CONTACT

13834589444; zqzhao69@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: March 15, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Within six months after the study completed
• Access Criteria: Research site

Locations

CN (1)