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

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ClinicalTrials.gov Identifier: NCT04624958
Recruitment Status : Not yet recruiting
First Posted : November 12, 2020
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Qingqing Cai, Sun Yat-sen University

Study Description
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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).

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Newly-diagnosed Mantle Cell Lymphoma Drug: Zanubrutinib and Rituximab Drug: R-DHAOx Drug: Zanubrutinib Maintenance Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: zanubrutinib, rituximab, consolidation chemotherapy and zanubrutinb maintenance

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
Zanubrutinb 160mg PO BID d1-28; Rituximab 375mg/m2 iv.drip d1.
Other Name: PART A

Drug: R-DHAOx
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.
Other Name: PART B

Drug: Zanubrutinib Maintenance
Zanubrutinb 160mg PO BID.


Outcome Measures
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Primary Outcome Measures :
  1. Complete remission rate after PART A [ Time Frame: 3 years ]
    Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.


Secondary Outcome Measures :
  1. Complete remission rate after study treatment [ Time Frame: 3 years ]
    Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.

  2. Objective Response rate [ Time Frame: 3 years ]
    Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.

  3. Progression Free Survival [ Time Frame: 5 years ]
    The time from the start of treatment to the progression of the tumor or death (due to any cause).

  4. Overall Survival [ Time Frame: 5 years ]
    The time from the start of treatment to time of death (due to any cause).

  5. Time to Response [ Time Frame: 3 years ]
    The time from the start of treatment to the first assessment of complete remission or partial remission.

  6. Duration of Response [ Time Frame: 5 years ]
    The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause).

  7. Percentage of Participants With Adverse Events [ Time Frame: 3 years ]
    Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04624958


Contacts
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Contact: Qingqing Cai, MD 0086-20-87342823 caiqq@sysucc.org.cn

Locations
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China, Guangdong
Guangdong General Hospital
Guangzhou, Guangdong, China, 510000
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China, 510060
Contact: Qingqing Cai, MD         
The First Affiliated Hospital of Guangdong Pharmaceutical University
Guangzhou, Guangdong, China, 510060
Sponsors and Collaborators
Sun Yat-sen University
Investigators
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Principal Investigator: Qingqing Cai, MD Sun Yat-sen University
More Information
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Responsible Party: Qingqing Cai, Chief physician, Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT04624958    
Other Study ID Numbers: B2020-232-01
First Posted: November 12, 2020    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
 Zanubrutinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action