Ibrutinib in Treating Patients With Relapsed or Refractory Transformed Indolent B-cell Non-Hodgkin Lymphoma

Phase 2

Completed

Conditions: Recurrent Transformed B-Cell Non-Hodgkin Lymphoma
Refractory Transformed B-Cell Non-Hodgkin Lymphoma

Interventions: Drug: Ibrutinib
Other: Laboratory Biomarker Analysis

Registration Number: NCT02207062

Lead Sponsor: University of Washington

Brief Summary: This pilot phase II trial studies ibrutinib in treating patients with transformed indolent (a type of cancer that grows slowly) B-cell non-Hodgkin lymphoma that have returned after a period of improvement (relapsed) or do not respond to treatment (refractory). Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes (proteins) needed for cell growth.

Detailed Description: OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Patients must have histologically confirmed transformed indolent B-cell non-Hodgkin lymphoma that is relapsed or refractory to at least one line of therapy
Patients must have a computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scan of the chest, abdomen, and pelvis within 28 days of enrollment
Patients must have measurable disease defined as lesions greater than 1.5 cm that can be accurately measured in two dimensions by CT (preferred), or MRI
Patients must have a positron emission tomography (PET) scan within 56 days of enrollment
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Absolute neutrophil count (ANC) >= 1000/mm^3 or >= 750/mm^3 in the setting of marrow involvement by disease
Platelets >= 50,000/mm^3 or >= 30,000/mm^3 in the setting of marrow involvement by disease or splenomegaly due to disease
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
Total bilirubin =< 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
Creatinine clearance (Clcr) > 25 mL/min
Patients must be anticipated to complete 2 cycles of therapy in the opinion of the treating physician
Women of childbearing potential and men who are sexually active must affirm they are practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during or after the study; for females, these restrictions apply for 1 month after the last dose of study drug; for males, these restrictions apply for 3 months after the last dose of the study drug
Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study
Sign (or their legally-acceptable representatives must sign) an informed consent document in accordance with institutional and federal guidelines indicating that they understand the investigational nature of and procedures required for the study, including biomarkers, and are willing to participate in and comply with the guidelines of the study

Exclusion Criteria

Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection
Major surgery or a wound that has not fully healed within 4 weeks of initiation of therapy
Known central nervous system lymphoma
History of stroke or intracranial hemorrhage within 6 months of screening
Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)
Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
Vaccinated with live, attenuated vaccines within 4 weeks of initiation of therapy
Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol sponsor-investigator/lead-sub-investigator
Patients that previously were treated with ibrutinib for > 7 days
Previous chemotherapy, immunotherapy, biologically targeted therapy, other investigational agent, or radiation therapy within 3 weeks of initiation of ibrutinib therapy or radio-immunotherapy within 12 weeks of initiation of ibrutinib therapy
Prior allogeneic transplant with graft-versus-host disease (GVHD) requiring immunosuppressive therapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (ibrutinib)	Laboratory Biomarker Analysis	Patients receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity.
Treatment (ibrutinib)	Ibrutinib	Patients receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (Combined Complete Response + Partial Response)	Up to 5 years

Secondary Outcome Measures

Name	Time	Method
Complete Response Rate	Up to 5 years
Disease Control Rate	>12 months
Tolerability of Chronic Ibrutinib Therapy	Up to 5 years	The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to classify and grade toxicities. Count of participants who stopped ibrutinib due to toxicities.
Overall Survival	Up to 5 years
Progression-free Survival	Time from first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years	Progression-free survival will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).
Response Rate Relative to the Underlying B-cell Histology	Up to 5 years	Participants with a histology of follicular lymphoma at diagnosis achieving at least a partial response to treatment.