Clinical Trials /

Ibrutinib With or Without Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

NCT02007044

Description:

This randomized phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether ibrutinib is more effective with or without rituximab in treating chronic lymphocytic leukemia.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib With or Without Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia
  • Official Title: Randomized Study of Ibrutinib Versus Ibrutinib Plus Rituximab (i Versus iR) in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL)

Clinical Trial IDs

  • ORG STUDY ID: 2013-0703
  • SECONDARY ID: NCI-2014-00989
  • SECONDARY ID: NCI-2014-00843
  • SECONDARY ID: 2013-0703
  • NCT ID: NCT02007044

Conditions

  • Prolymphocytic Leukemia
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Arm I (ibrutinib)
RituximabABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83Arm II (ibrutinib, rituximab)

Purpose

This randomized phase II trial studies ibrutinib with or without rituximab in treating patients with chronic lymphocytic leukemia that has come back after treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether ibrutinib is more effective with or without rituximab in treating chronic lymphocytic leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare the 2-year progression-free survival (PFS) rate in treated patients.

      SECONDARY OBJECTIVES:

      I. To determine safety and tolerability, the overall response rate (ORR), the estimated PFS,
      changes in immune parameters (lymphocyte subpopulations, immunoglobulin levels) and biomarker
      responses in relapsed chronic lymphocytic leukemia (CLL) patients receiving ibrutinib (i)
      versus ibrutinib and rituximab (iR).

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat
      every 28 days in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive
      rituximab intravenously (IV) over 3-8 hours on days 1, 8, 15, and 22 of course 1 and day 1 of
      courses 2-6. Courses repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 60 days and then every 4
      months for 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (ibrutinib)ExperimentalPatients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Ibrutinib
Arm II (ibrutinib, rituximab)ExperimentalPatients receive ibrutinib as in Arm I beginning on day 1 or 2. Patients also receive rituximab IV over 3-8 hours on days 1, 8, 15, and 22 of course 1 and day 1 of courses 2-6. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Ibrutinib
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a diagnosis of CLL/small lymphocytic lymphoma (SLL) or
             prolymphocytic leukemia (PLL) and be previously treated; given the poor outcome of
             CLL/SLL/PLL patients with 17p deletion (del) or tumor protein (TP)53 mutation to
             standard frontline chemo-immunotherapy, such patients will be eligible if they are
             untreated

          -  Patients must have an indication for treatment by 2008 International Workshop on
             Chronic Lymphocytic Leukemia (IWCLL) criteria

          -  Patient must understand and voluntarily sign an informed consent, and be able to
             comply with study procedures and follow-up examinations

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  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

          -  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

          -  Alanine aminotransferase (ALT) =< 2.5 x ULN

          -  Estimated creatinine clearance (CrCl) of > 30 mL/min, as calculated by the
             Cockcroft-Gault equation unless disease related

          -  Free of prior malignancies for 3 years with exception of patients diagnosed with basal
             cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or
             breast, who are eligible even if they are currently treated or have been treated
             and/or diagnosed in the past 3 years prior to study enrolment; 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 at MD Anderson Cancer Center

          -  A urine pregnancy test (within 7 days of enrollment date) is required for women with
             childbearing potential

        Exclusion Criteria:

          -  Pregnant or breast-feeding females

          -  Prior therapy with ibrutinib or other kinase inhibitors that target Bruton's tyrosine
             kinase (BTK); patients who previously received therapy with the phosphoinositide-3
             kinase (PI3K) delta inhibitor idelalisib (Zydelig) are allowed to be enrolled

          -  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

          -  Investigational agent received within 30 days prior to the first dose of study drug

          -  Systemic fungal, bacterial, viral, or other infection not controlled (defined as
             exhibiting ongoing signs/symptoms related to the infection and without improvement,
             despite appropriate antibiotics or other treatment)

          -  Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune
             thrombocytopenia (ITP)

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

          -  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 ibrutinib and rituximab

          -  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

          -  History of stroke or cerebral hemorrhage within 6 months

          -  Evidence of bleeding diathesis or coagulopathy within 3 months

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to enrollment date, anticipation of need for major surgical procedure during the
             course of the study

          -  Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to enrollment date; bone marrow aspiration and/or biopsy are allowed

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

          -  Treatment with Coumadin; patients who recently received Coumadin must be off Coumadin
             for at least 7 days prior to start of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival rate
Time Frame:Time from start of treatment to progression or death date, assessed at 2 years
Safety Issue:
Description:A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 5 years
Safety Issue:
Description:Toxicity will be reported by type, frequency and severity. Highest toxicity grades per patient per course will be tabulated for selected adverse events and laboratory measurements.
Measure:Overall response rate
Time Frame:Up to 5 years
Safety Issue:
Description:Fisher's exact test and Wilcoxon rank test will be used in the data analyses of continuous variables.
Measure:Estimated progression-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:Time to progression functions will be estimated using the Kaplan-Meier method. A two-sided log-rank test will be used to assess the differences of progression-free survival between the treatment groups.
Measure:The changes in the immune parameters in the lymphocyte subpopulations.
Time Frame:Baseline to up to 5 years
Safety Issue:
Description:Will be assessed by flow cytometry.
Measure:The changes in immune parameters in the immunoglobulin levels
Time Frame:Baseline to up to 5 years
Safety Issue:
Description:Will be assessed by flow cytometry
Measure:Quality of life (QOL)
Time Frame:Up to 24 courses (96 weeks)
Safety Issue:
Description:Will be assessed by the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30). Analyzed by linear mixed models for longitudinal data. These models allow each patient to have a random intercept and a random slope, which describe their differences at baseline and their different changing trends over time.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

April 29, 2021