Clinical Trials /

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

NCT04624958

Description:

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).

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Zanubrutinib and Rituximab Followed by R-DHAOx Then Maintenance With Zanubrutinib for Newly-Diagnosed MCL
  • Official Title: Zanubrutinib and Rituximab Followed by R-DHAOx (Rituximab, Dexamethasone, Cytarabine and Oxaliplatin) Regimen Then Maintenance With Zanubrutinib for Newly-Diagnosed Mantle Cell Lymphoma (MCL): a Single Arm, Open Label, Multi-center Phase II Study

Clinical Trial IDs

  • ORG STUDY ID: B2020-232-01
  • NCT ID: NCT04624958

Conditions

  • Mantle Cell Lymphoma
  • Newly-diagnosed Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
Zanubrutinib and RituximabPART Azanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance
R-DHAOxPART Bzanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance
Zanubrutinib Maintenancezanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenanceExperimentalPart 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.
  • Zanubrutinib and Rituximab
  • R-DHAOx
  • Zanubrutinib Maintenance

Eligibility Criteria

        Inclusion Criteria:

          -  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);

        Exclusion Criteria:

          -  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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission rate after PART A
Time Frame:3 years
Safety Issue:
Description:Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.

Secondary Outcome Measures

Measure:Complete remission rate after study treatment
Time Frame:3 years
Safety Issue:
Description:Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measure:Objective Response rate
Time Frame:3 years
Safety Issue:
Description:Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.
Measure:Progression Free Survival
Time Frame:5 years
Safety Issue:
Description:The time from the start of treatment to the progression of the tumor or death (due to any cause).
Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description:The time from the start of treatment to time of death (due to any cause).
Measure:Time to Response
Time Frame:3 years
Safety Issue:
Description:The time from the start of treatment to the first assessment of complete remission or partial remission.
Measure:Duration of Response
Time Frame:5 years
Safety Issue:
Description:The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause).
Measure:Percentage of Participants With Adverse Events
Time Frame:3 years
Safety Issue:
Description:Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sun Yat-sen University

Last Updated

November 12, 2020