Clinical Trials /

BTK Inhibitor Zanubrutinib (BGB-3111) in Combination With Rituximab for Previously Untreated Patient

NCT04458610

Description:

This is a Phase II clinical trial of limited-duration therapy with zanubrutinib (BGB-3111) in combination with rituximab for patients with treatment-naive CLL.

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BTK Inhibitor Zanubrutinib (BGB-3111) in Combination With Rituximab for Previously Untreated Patient
  • Official Title: BTK Inhibitor Zanubrutinib (BGB-3111) in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL)

Clinical Trial IDs

  • ORG STUDY ID: 2019-0012
  • NCT ID: NCT04458610

Conditions

  • Chronic Lymphocytic Leukemia (CLL)

Interventions

DrugSynonymsArms
BGB-3111
Rituximab

Purpose

This is a Phase II clinical trial of limited-duration therapy with zanubrutinib (BGB-3111) in combination with rituximab for patients with treatment-naive CLL.

Detailed Description

      The primary objective is to determine the proportion of patients who have treatment-free
      remission 6 months after discontinuation of zanubrutinib. Treatment-free remission will be
      defined as the time from discontinuation of zanubrutinib to the date of CLL relapse with
      active disease, as defined by the CLL criteria 1. The outcome of this trial will be
      considered positive if more than 70% of patients remain in treatment-free remission 6 months
      after zanubrutinib discontinuation. This estimation is based on a prior analysis of the
      outcome of CLL patients who discontinued BTK inhibitor (BTKi) therapy with ibrutinib because
      of drug intolerance, and were in complete or partial remission2. In these analyses,
      approximately 75% of patients remained in remission after ibrutinib discontinuation for
      ibrutinib intolerance.

      Secondary objectives are

        -  to determine clinical factors associated with a treatment-free remission of more than 6
           months after discontinuation of zanubrutinib;

        -  to determine the treatment-free remission length;

        -  to evaluate the efficacy of re-treatment with zanubrutinib plus rituximab in patients
           who relapse.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          -  Patients will be eligible for inclusion in the study if they meet all of the following
             criteria:

               1. Patients must have a diagnosis CLL/SLL and be previously untreated.

               2. Patients must have an indication for treatment by 2018 IWCLL Criteria1.

               3. Patients must be age >/= 18 years at the time of signing informed consent,
                  understand and voluntarily sign an informed consent, and be able to comply with
                  study procedures and follow-up examinations.

               4. ECOG performance status of 0-2.

               5. Patients of childbearing potential must be willing to practice highly effective
                  birth control (e.g., condoms, implants, injectables, combined oral
                  contraceptives, intrauterine devices [IUDs], sexual abstinence, or sterilized
                  partner) during the study and for 30 days after the last dose of study drug.
                  Women of childbearing potential include any female who has experienced menarche
                  and who has not undergone successful surgical sterilization (hysterectomy,
                  bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal.

               6. Adequate renal and hepatic function as indicated by all of the following: Total
                  bilirubin </=1.5 x institutional Upper Limit of Normal (ULN) except for patients
                  with bilirubin elevation due to Gilbert's disease who will be allowed to
                  participate; an ALT </=2.5 x ULN; and an estimated creatinine clearance (CrCl) of
                  > 30 mL/min, as calculated by the Cockcroft- Gault equation unless disease
                  related.

               7. Free of prior malignancies for 3 years with exception of currently treated basal
                  cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
                  or breast. If patients have another malignancy that was treated within the last 3
                  years, such patients can be enrolled, after consultation with the Principal
                  Investigator, if the likelihood of requiring systemic therapy for this other
                  malignancy within 2 years is less than 10%, as determined by an expert in that
                  particular malignancy.

               8. A Urine Pregnancy Test (within 7 days of Day 1) is required for women with
                  childbearing potential.

        Exclusion Criteria:

          1. Pregnant or breast-feeding females.

          2. Prior therapy with zanubrutinib or other kinase inhibitors that target BCR signaling
             (such as ibrutinib, idelalisib).

          3. Prior CLL-directed treatment including chemotherapy, chemo-immunotherapy, monoclonal
             antibody therapy, radiotherapy, high-dose corticosteroid therapy (more than 60 mg
             Prednisone daily or equivalent), or immunotherapy within 21 days prior to enrollment
             or concurrent with this trial. Patients that receive zanubrutinib salvage therapy
             cannot have received any other CLL-directed therapy besides frontline zanubrutinib
             plus rituximab.

          4. Investigational agent received within 30 days prior to the first dose of study drug.
             If received any investigational agent prior to this time point, drug-related
             toxicities must have recovered to Grade 1 or less prior to first dose of study drug.

          5. Systemic fungal, bacterial, viral, or other infection not controlled by antimicrobial
             therapy, in the assessment of the treating physician(s) and/or the principal
             investigator.

          6. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
             thrombocytopenia (ITP), i.e. with laboratory signs of active hemolysis or
             thrombocytopenia, requiring support with blood products and/or with rapid decline in
             hemoglobin (>1 gram/dL per day) or platelet counts (>10,000/uL per day).

          7. Patients with severe hematopoietic insufficiency, as defined by an absolute neutrophil
             count of less than 500/μL, unless disease-related, and/or a platelet count of less
             than 30,000/μL at time of screening for this protocol.

          8. Any other severe concurrent disease, or have a history of serious organ dysfunction or
             disease involving the heart, kidney, liver or other organ system that may place the
             patient at undue risk to undergo therapy with zanubrutinib and rituximab.

          9. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
             congestive heart failure, or myocardial infarction within 6 months of screening, or
             any Class 3 or 4 cardiac disease as defined by the New York Heart Association
             Functional Classification. Patients with a history of paroxysmal atrial fibrillation
             (PAF) or deep vein thrombosis or pulmonary embolism (DVT/PE) can be included if they
             had no signs of PAF or DVT/PE in the last 6 months before enrolment. Patients with
             ongoing atrial fibrillation (AFib) or ongoing PAF or DVT/PE should be excluded.

         10. History of stroke or cerebral hemorrhage within 6 months.

         11. Evidence of bleeding diathesis or coagulopathy within 3 months.

         12. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 1, anticipation of need for major surgical procedure during the course of
             the study.

         13. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to Day 1. Bone marrow aspiration and/or biopsy are allowed.

         14. Serious, non-healing wound, ulcer, or bone fracture.

         15. Treatment with warfarin (Coumadin®) or any other vitamin K antagonist. Patients who
             recently received warfarin must be off warfarin for at least 7 days prior to start of
             the study. Patients receiving novel oral anticoagulant (NOAC), also termed direct oral
             anticoagulant (DOAC) are permitted to enroll. Patients who are currently on a vitamin
             K antagonist must be switched to a non-vitamin K antagonist, such as a NOAC/DOAC.

         16. Patients with active Hepatitis B (HBV) or Hepatitis C

         17. Patients with known HIV infection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Number of participants with treatment-free remission
Time Frame:Up to 6 months
Safety Issue:
Description:To determine the proportion of patients who have treatment-free remission 6 months after discontinuation of zanubrutinib. Treatment-free remission will be defined as the time from discontinuation of zanubrutinib to the date of CLL relapse with active disease, as defined by the CLL criteria1. The outcome of this trial will be considered positive if more than 70% of patients remain in treatment-free remission 6 months after zanubrutinib discontinuation.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

July 6, 2020