The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus rituximab in adult Asia Pacific region patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known) study designed to evaluate the efficacy and safety of ibrutinib versus rituximab in adult Asia Pacific region patients with relapsed/refractory CLL or SLL with active disease requiring treatment who have failed at least 1 prior line of therapy and are not considered appropriate candidates for treatment or retreatment with purine analog-based therapy. Approximately 150 patients will be randomly assigned in a 1:2 ratio into 2 treatment arms to receive either intravenous rituximab (Treatment Arm A) for 6 cycles or oral ibrutinib (Treatment Arm B) until disease progression or unacceptable toxicity, whichever occurs first. The study will include screening, treatment, and follow-up phases. Treatment will extend from randomization until study drug discontinuation. Follow-up will consist of 2 phases: post-treatment (from the discontinuation of treatment for reasons other than disease progression until the patient has progressive disease) and post-disease progression (subsequent anticancer therapy and survival status will be recorded until death, lost to follow-up, consent withdrawal, or study closure). Patients in the rituximab arm with disease progression or who meet the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for requiring subsequent anti-CLL therapy may be considered for cross over to receive ibrutinib 420 mg orally, daily until disease progression, unacceptable toxicity, withdrawal from study, or until study end whichever occurs earliest. Efficacy evaluations will assess for disease response and progression in accordance with International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Serial pharmacokinetic (study of what a drug does to the body) blood samples will be collected in the ibrutinib treatment group. Safety will be assessed throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
Up to 6 cycles (total of 8 doses administered by intravenous infusion): 375 mg/m2 on Day 1 of Cycle 1, 500 mg/m2 on Day 15 of Cycle 1 (Weeks 1-4); 500 mg/m2 on Day 1 and Day 15 of Cycle 2 (Weeks 5-8); and 500 mg/m2 on Day 1 of Cycles 3-6 (Weeks 9-24).
420 mg capsules administered by mouth daily until disease progression or unacceptable toxicity, whichever occurs first.
Unnamed facility
Concord, Australia
Unnamed facility
Gosford, Australia
Unnamed facility
Progression-free Survival (PFS)
Progression-free survival was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for progressive disease (PD): New enlarged nodes greater than (\>)1.5 centimeter (cm), new hepatomegaly or splenomegaly, or other organ infiltrates; greater than or equal to (\>=)50 percent (%) increase from nadir in existing lymph node or \>=50% increase from nadir in sum of product of diameters of multiple nodes; \>=50% increase from nadir in enlargement of liver or spleen; \>=50% increase from baseline in lymphocyte count (and to \>=5\*10\^9/L) unless considered treatment-related lymphocytosis; New cytopenia (Hemoglobin b \[Hgb\] or platelets) attributable to chronic lymphocytic leukemia (CLL) and transformation to a more aggressive histology.
Time frame: From the date of randomization to the date of disease progression or death, whichever was first reported (Up to 3.7 years)
Overall Response Rate (ORR)
ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils \>1.5\*10\^9/liter (L), platelets \>100\*10\^9/L, Hgb \>11 gram per deciliter (g/dL) and absolute lymphocyte count \<4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR- \>=50% drop in lymphocyte count from baseline or \<=4.0\*10\^9/L with following: \>=50% decrease in sum products of up to 6 lymph nodes, no new enlarged lymph nodes, When abnormal, \>=50% decrease in enlargement of spleen from baseline or normalization and a response in 1 of following: Neutrophils \>1.5\*10\^9/L, Platelets\>100000/mcL and Hgb\>11 g/dL or \>=50% improvement over baseline in all.
Time frame: From the date of randomization to disease progression (Up to 3.7 years)
Overall Survival (OS)
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Heidelberg, Australia
Unnamed facility
Perth, Australia
Unnamed facility
Tweed Heads, Australia
Unnamed facility
Beijing, China
Unnamed facility
Chendu, China
Unnamed facility
Fuzhou, China
Unnamed facility
Guangzhou, China
Unnamed facility
Jinan, China
...and 16 more locations
Overall survival was defined as the interval between the date of randomization and the date of death from any cause.
Time frame: From the date of randomization to the date of death (Up to 3.7 years)
Number of Participants With Sustained Hematologic Improvement
Sustained hematologic improvement was defined as hematological improvement that was sustained continuously for greater than or equal to (\>=) 56 days without blood transfusion or growth factors: 1) Platelet counts greater than (\>)100\* 109/liter (L) if baseline less than or equal to (\<=) 100\*109/L or increase \>= 50 percent (%) over baseline; 2) Hemoglobin \>11 gram per deciliters (g/dL) if baseline \<= 11 g/dL or increase \>= 2 g/dL over baseline.
Time frame: From the date of randomization to disease progression (Up to 3.7 years)
Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms
The most common disease-related symptoms associated with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (fatigue, weight loss, fevers, night sweats, and abdominal discomfort/splenomegaly) were reported by grade.
Time frame: From the date of randomization to disease progression (Up to 3.7 years)