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

Phase 2

Not yet recruiting

• Conditions: Mantle Cell Lymphoma
• Interventions: Drug: Zanubrutinib and RCHOP/RDHAP

• Registration Number: NCT06255704
• Lead Sponsor: Shanxi Province Cancer Hospital

Brief Summary

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

Detailed Description

A single-arm, single-center, open-label phase II study of Zanubrutinib combined with R-CHOP/R-DHAP alternating induction therapy followed by Zanubrutinib rituximab maintenance therapy.The primary objective of this study was to assess CR and ORR rates after 6 cycles of initiation (i.e., at the end of induction therapy), and to collect adverse events during induction and maintenance therapy.

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-05
• Study First Submitted QC: 2024-02-12
• Last Update Submitted: 2024-02-12
• Study First Posted: 2024-02-13
• Last Update Posted: 2024-02-13
• Study Start: 2024-03-15
• Primary Completion: 2026-01-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• 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)
• 1. Neutrophils ≥1×109/L within 7 days prior to study entry, and no growth factor support therapy.
• 2. Platelets ≥75×109/L within 7 days prior to study entry without growth factor support or blood transfusion.
• 3. 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)
• 4. Creatinine clearance ≥30ml/min
• 5. 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
• Life expectancy > 3 months.
• Written informed consent form according to GCP and national regulations.

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Zanubrutinib and RCHOP/RDHAP	Zanubrutinib and RCHOP/RDHAP	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

Primary Outcome Measures

Name	Time	Method
CR rate after 6 cycles of induction therapy	18 weeks	To evaluate the CR rate after Zanubrutinib-based induction therapy in subjects with newly diagnosed MCL.

Secondary Outcome Measures

Name	Time	Method
duration of response, DOR	60 weeks	Defined as the time after the start of treatment from the first time remission criteria are met until disease progression or death is objectively recorded, whichever occurs first.
Overall survival (OS)	60 weeks	The time from start of treatment to death from any cause
ORR rate after 6 cycles of induction therapy	18 weeks	To evaluate the ORR rate after Zanubrutinib-based induction therapy in subjects with newly diagnosed MCL.
Progression free survival (PFS)	60 weeks	The time from start of treatment to progression or death from any cause
MRD negative rate at the end of induction therapy	18 weeks	MRD negative rate in peripheral blood or bone marrow at the end of induction therapy

Trial Locations

Locations (1)

Hematology Department of ShanXi Cancer Hospital; 🇨🇳 Taiyuan, Shanxi, China