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

A Pilot Study of Single-Agent Ibrutinib in Relapsed or Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Transformed B-Cell Non-Hodgkin Lymphoma; Refractory Transformed B-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Ibrutinib

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (ibrutinib); Patients receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ibrutinib; Given PO; Other Names: PCI-32765; BTK Inhibitor PCI-32765; CRA-032765

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (Combined Complete Response + Partial Response)	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Up to 5 years
Complete Response Rate		Up to 5 years
Disease Control Rate		>12 months
Progression-free Survival	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).	Time from first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
Response Rate Relative to the Underlying B-cell Histology	Participants with a histology of follicular lymphoma at diagnosis achieving at least a partial response to treatment.	Up to 5 years
Tolerability of Chronic Ibrutinib Therapy	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.	Up to 5 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Janssen Pharmaceuticals
• Investigators: Principal Investigator: Ajay K. Gopal, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): November 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimated): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Ibrutinib
• Other Study ID Numbers: 9107 (Fred Hutch/University of Washington Cancer Consortium); NCI-2014-01573 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RG1714041 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO