Zanubrutinib and Rituximab Followed by R-DHAOx Then Maintenance with Zanubrutinib for Newly-Diagnosed MCL

NCT04624958 | Active Not Recruiting Phase 2

• 1 other identifier: B2020-232-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

This phase 2 trial studies the efficacy and safety of zanubrutinib plus rituximab followed by R-DHAOx (rituximab, dexamethasone, cytarabine and oxaliplatin) regimen then maintenance with zanubrutinib for newly-diagnosed Mantle Cell Lymphoma (MCL).

Conditions

Mantle Cell Lymphoma; Newly-diagnosed Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete remission rate after PART A

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

  3 years

Secondary Outcomes (7)

• Complete remission rate after study treatment

  3 years

• Objective Response rate

  3 years

• Progression Free Survival

  5 years

• Overall Survival

  5 years

• Time to Response

  3 years

Study Arms (1)

zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

EXPERIMENTAL

Part A (Zanubrutinib and Rituximab): Patients receive zanubrutinib on days 1-28 and rituximab on day 1. Treatment cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve CR. PART B (Consolidation chemotherapy of R-DHAOx): Patients receive R-DHAOx regimen every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Elderly patients (\> 65 years old) and patients who achieved CR and minimal residual disease negative after PART B receive zanubrutinb maintenance therapy. Young patients (\<65 years old) who achieved CR but minimal residual disease positive after PART B can receive autologous stem cell transplantation and then zanubrutinb maintenance therapy. Patients with PD, SD or PR after PART B quit the trial. ZANUBRUTINB MAINTENANCE: Patients receive zanubrutinib every day for up to one year.

Drug: Zanubrutinib and Rituximab; Drug: R-DHAOx; Drug: Zanubrutinib Maintenance

Interventions

Zanubrutinib and Rituximab DRUG

Zanubrutinb 160mg PO BID d1-28; Rituximab 375mg/m2 iv.drip d1.

Also known as: PART A

zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

R-DHAOx DRUG

Rituximab 375mg/m2 iv.drip d1; Dexamethasone 20mg iv.drip d1-4; Cytarabine 2000mg/m2 (1000mg/m2 for patients aged over 65) iv.drip d2,3 Oxaliplatin 130mg/m2 iv.drip d1.

Also known as: PART B

zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

Zanubrutinib Maintenance DRUG

Zanubrutinb 160mg PO BID.

zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed CD20 positive mantle cell lymphoma;
• Patients with MCL-related symptomatic and need immediate therapy; Include any of the following: (1) Blastoid variant (2) Pleomorphic variant (3) Ki-67 ≥30% (4) Bulky mass \> 7 cm or ≥2 tumors, each ≥5 cm in diameter (5) Mutations in TP53, c-MYC or NOTCH genes (6) Size of spleen ≥20 cm (7) Lymphoma B symptoms (8) Mantle Cell International Prognostic Score (MIPI) \> 3 (9) Lymphoma threatening organ function (10) Elevated lactate dehydrogenase (11) Peripheral blood white blood cell \> 50×10\^9/L (12) Pancytopenia due to bone marrow involvement (13) Pain due to lymphoma;
• Patients received no prior anti-lymphoma treatment;
• At least one evaluable lesion according to 2014 Lugano criteria;
• Ann Arbor stage II-IV;
• Eastern Cooperative Oncology Group (ECOG) of 0-2;
• Life expectancy \> 3 months;
• Able to participate in all required study procedures;
• Proper functioning of the major organs: 1) The absolute value of neutrophils (\>1.5×10\^9/L); 2) platelet count (\> 75×10\^9/L); 3) Hemoglobin (\> 80 g/L); 4) Serum creatinine \<1.5 times Upper Limit Normal (ULN) ; 5) Serum total bilirubin \< 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \< 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) \< 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range at screening time);

You may not qualify if:

• Involvement of central nervous system (CNS)
• Patients with Hemophagocytic syndrome;
• Patients with active bleeding, bleeding tendency or require anticoagulation treatment;
• Patients require treatment with strong CYP3A inhibitors;
• Uncontrolled active infection, with the exception of tumor-related B symptom fever;
• History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known;
• Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;
• Diagnosed with or receiving treatment for malignancy other than lymphoma;
• Pregnant or breastfeeding women;
• Other researchers consider it unsuitable for patients to participate in this study.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (3)

Guangdong General Hospital

Guangzhou, Guangdong, 510000, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

The First Affiliated Hospital of Guangdong Pharmaceutical University

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

zanubrutinib; Rituximab; Medicare Part B

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Medicare; Medical Assistance; Public Assistance; Financing, Government; Financing, Organized; Economics; Health Care Economics and Organizations; Insurance, Health; Insurance; Legislation as Topic; Social Control, Formal

Study Officials

• Qingqing Cai, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: November 12, 2020
• Study Start: December 1, 2020
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 18, 2024

Record last verified: 2024-10

Locations

CN (3)