A Study of PCI-32765 (Ibrutinib) Versus Rituximab in Relapsed or Refractory Chronic Leukemia/Lymphoma

Janssen (J&J Innovative Medicine)

Status and phase

Completed

Phase 3

Conditions

Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia

Treatments

Drug: Ibrutinib

Drug: Rituximab

Study type

Interventional

Funder types

Industry

Identifiers

NCT01973387

CR102604

PCI-32765CLL3002 (Other Identifier)

Details and patient eligibility

About

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).

Full description

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.

Enrollment

160 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Eastern Cooperative Oncology Group performance status of 0-1
Diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
Laboratory values within protocol-defined parameters
Active disease meeting International Workshop on Chronic Lymphocytic Leukemia 2008 criteria
Received at least 1 prior therapy for CLL/SLL and not appropriate for treatment or retreatment with purine analog-based therapy
Measurable nodal disease by computed tomography
Female subjects of childbearing potential must have a negative serum or urine pregnancy test at Screening and agree to use highly effective methods of contraception during the study and for 90 days following the last dose with ibrutinib or 12 months following the last dose of rituximab

Exclusion criteria

Central nervous system lymphoma or leukemia
Prolymphocytic leukemia or history of or currently suspected Richter's transformation
Refractory to prior rituximab-based therapy
Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days prior to first dose of study drug
Corticosteroid use >20 mg within 1 week prior to first dose of study drug
Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose of study drug
Prior autologous transplant within 6 months prior to first dose of study drug
Prior allogeneic stem cell transplant
Major surgery within 4 weeks prior to first dose of study drug
History of prior malignancy according to protocol-defined criteria
Currently active clinically significant cardiovascular disease within 6 months prior to first dose with study drug
Uncontrolled active systemic fungal, bacterial, viral, or other ongoing anti-infective treatment administered intravenously
History of human immunodeficiency virus or active infection with hepatitis B or C
History of stroke or intracranial hemorrhage within 6 months prior to random assignment
Pregnant or lactating women
Current life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, or put the study at risk
Requires or receiving anticoagulation with warfarin or equivalent Vitamin K antagonists
Requires treatment with a strong CYP3A4/5 inhibitor
Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (greater than [>]20 milligram [mg] daily of prednisone daily or equivalent)