A Study to Evaluate the Efficacy and Safety of Ibrutinib, in Patients With Mantle Cell Lymphoma Who Progress After Bortezomib Therapy

Mantle Cell Lymphoma Clinical Trial

Official title:

A Phase 2, Multicenter, Single-Arm, Study to Evaluate the Efficacy and Safety of Single-Agent Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Mantle Cell Lymphoma Who Progress After Bortezomib Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01599949
• Other study ID #: CR100847
• Secondary ID: PCI-32765MCL2001
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2012
• Last updated: May 27, 2016
• Start date: August 2012
• Est. completion date: May 2015

Study information

• Verified date: May 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal GovernmentGreat Britain: Medicines and Healthcare Products Regulatory AgencyGreat Britain: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of ibrutinib in patients with mantle cell lymphoma who received at least 1 prior rituximab-containing chemotherapy regimen and who progressed after bortezomib therapy.

Description:

This is a single-arm (all patients will receive the study drug) study to evaluate the efficacy and safety of ibrutinib in patients with mantle cell lymphoma (MCL) who have received at least 1 rituximab-containing chemotherapy regimen and who progressed after bortezomib therapy. Approximately 110 eligible patients will be enrolled. During the treatment phase, patients will receive 560 mg of ibrutinib by mouth once daily continuously until disease progression, unacceptable toxicity, or study end, whichever occurs first. Treatment will be continuous (without interruption) and self-administered at home. Doses can be held or reduced based on the severity of and the recovery from side effects of the study drug. The sponsor will ensure that patients benefiting from treatment with ibrutinib will be able to continue treatment after the end of the study. Data will be collected on disease response to the treatment, on progression-free survival, overall survival, and subsequent anti-MCL therapies. Serial pharmacokinetic (study of what the body does to a drug) samples will be collected as detailed in the protocol. Safety will be monitored throughout the study. An interim analysis of the pharmacokinetic data will occur approximately 3 months after the scheduled pharmacokinetic sampling in Cycles 1 and 2 has been completed. Data will be analyzed 1 year after the last patient is enrolled for the primary analysis and 2 years after last patient is enrolled for the final follow-up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of confirmed mantle cell lymphoma (MCL) with at least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma

• Must have received at least 1 prior rituximab-containing chemotherapy regimen, but no more than 5 prior regimens

• Must have received at least 2 cycles of bortezomib therapy (single-agent or in combination) and have documented progressive disease during or after bortezomib therapy

• Eastern Cooperative Oncology Group performance status score 0, 1, or 2

• Hematology and biochemical values within protocol-defined parameters

Exclusion Criteria:

• Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of the first dose of study drug

• Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors

• More than 5 prior lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a >6 month treatment-free interval

• Known central nervous system lymphoma

• Diagnosed or treated for malignancy other than MCL, except malignancy treated with curative intent and with no known active disease present for >=3 years before the first dose of study drug and felt to be at low risk for recurrence by the treating physician, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, or adequately treated cervical carcinoma in situ without evidence of disease.

• History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug

• Requires anticoagulation with warfarin or equivalent vitamin K antagonists

• Requires treatment with strong CYP3A4/5 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

• Known history of human immunodeficiency virus or active infection with hepatitis C virus or hepatitis B virus or any uncontrolled active systemic infection

• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• Ibrutinib
Type=exact number, unit=mg, number=560, form=capsule, route=oral use. 560 mg oral ibrutinib is to be administered once daily continuously until disease progression, unacceptable toxicity, or study end, whichever occurs first. Doses can be held or reduced based on the severity of and the recovery from side effects of the study drug.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC	Pharmacyclics

Countries where clinical trial is conducted

United States,  Belgium,  France,  Israel,  Poland,  Puerto Rico,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate		1 year after the last patient is enrolled	No
Secondary	Overall survival rate		1 year after the last patient is enrolled and 2 years after the last patient is enrolled	No
Secondary	Progression-free survival rate		1 year after the last patient is enrolled and 2 years after the last patient is enrolled	No
Secondary	Mean change from baseline in the Lym subscale		1 year after the last patient is enrolled and 2 years after the last patient is enrolled	No
Secondary	Mean change from baseline in the EQ-5D-5L index		1 year after the last patient is enrolled and 2 years after the last patient is enrolled	No
Secondary	Mean plasma concentrations of ibrutinib		Up to Cycle 2, Day 21	No
Secondary	Maximum observed plasma concentration of ibrutinib		Up to Cycle 2, Day 21	No
Secondary	Minimum observed plasma concentration of ibrutinib		Up to Cycle 2, Day 21	No
Secondary	Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib		Up to Cycle 2, Day 21	No
Secondary	The number of participants affected by an adverse event		Up to 30 days after the last dose of study medication	Yes
Secondary	Overall response rate		1 year after the last patient is enrolled and 2 years after the last patient is enrolled	No

External Links

•   A Phase 2, Multicenter, Single-Arm Study to Evaluate the Efficacy and Safety of Single- Agent Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Subjects With Mantle Cell Lymphoma Who Progress After Bortezomib Therapy