Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Stage IV Chronic Lymphocytic Leukemia Clinical Trial

Official title: A Randomized Phase III Study of Bendamustine Plus Rituximab Versus Ibrutinib Plus Rituximab Versus Ibrutinib Alone in Untreated Older Patients (>/= 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

Status Active, not recruiting

Clinical Trial Summary

This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether rituximab with bendamustine hydrochloride may work better than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine whether progression free survival (PFS) is superior after therapy with bendamustine hydrochloride (bendamustine) in combination with rituximab, ibrutinib alone, or ibrutinib in combination with rituximab in patients age 65 or older with previously untreated chronic lymphocytic leukemia (CLL).

SECONDARY OBJECTIVES:

I. To determine 2-year PFS in each of the three treatment arms. II. To determine which treatment arm produces superior overall survival (OS). III. To determine the complete response (CR) rate, complete and nodular partial response (CR/nPR) rate, and overall response (PR+nPR+CR) rate (ORR) among the three treatment arms and compare these arms.

IV. To determine the impact of minimal residual disease (MRD)-negative disease at time of CR documentation and at 2 years on PFS and OS in each of the treatment arms.

V. To determine duration of response after each of the three treatments and compare these treatment arms.

VI. To determine toxicity and tolerability of the three treatment regimens. VII. To determine response and PFS of patients initially on the bendamustine in combination with rituximab arm who cross over to ibrutinib.

OTHER PRE-SPECIFIED OBJECTIVES:

I. To determine whether baseline cytogenetic markers, Zap-70 methylation, IgVH mutational status, or select deoxyribonucleic acid (DNA) mutations predict outcomes or time to response in these three arms.

II. To determine whether local fluorescence in situ hybridization (FISH) results for del(11q22.3) and del(17p13.1) are consistent with central analysis.

III. To determine whether baseline micro ribonucleic acid (RNA) and gene expression markers are correlated with clinical outcomes of interest (e.g. progression-free and alive at 2 years versus not), as well as to explore changes in microRNA expression from baseline to post-treatment time points, with a focus on those with persistent lymphocytosis and relapse.

IV. To determine whether eradication of MRD predicts longer duration of response with standard therapy and ibrutinib-based regimens.

V. To describe the baseline functional status, comorbid medical conditions, and number of medications of older CLL patients who meet criteria for therapy.

VI. To determine how functional status changes with therapy using baseline to 3-month evaluation and end-of-study/2-year evaluation; to determine whether this change is different among the treatment groups.

VII. To determine whether geriatric assessment variables known to be associated with chemotherapy toxicity in other disease groups can also predict therapy-associated toxicity in the CLL population.

VIII. To assess whether the FCGR3A polymorphism (rs396991) is correlated with depth of response (MRD status) to ibrutinib plus rituximab after 6 cycles, with secondary endpoints CR rate, rapidity of response, and progression-free survival (PFS).

IX. To assess whether C1QA polymorphism (rs172378) is correlated with MRD status, CR rate, rapidity of response, and PFS.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive rituximab intravenously (IV) on day 1 (day 0 course 1) and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover to Arm II.

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

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

After completion of study treatment, patients are followed up every 6 months for up to 10 years. ;

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Stage I Chronic Lymphocytic Leukemia
• Stage II Chronic Lymphocytic Leukemia
• Stage III Chronic Lymphocytic Leukemia
• Stage IV Chronic Lymphocytic Leukemia

• NCT number: NCT01886872
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 9, 2013
• Completion date: January 30, 2025