Clinical trial NCT01599949: A Study to Evaluate the Efficacy and Safety of Ibrutinib, in Patients With Mantle Cell Lymphoma Who Progress After Bortezomib Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Mantle cell lymphoma
Ibrutinib
Bruton's tyrosine kinase inhibitor
Rituximab
Bortezomib
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Pharmacyclics LLC.
First posted: 2012-05-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate
timeFrame: 1 year after the last patient is enrolled
Secondary outcomes:
measure: Overall survival rate
timeFrame: 1 year after the last patient is enrolled and 2 years after the last patient is enrolled
measure: Progression-free survival rate
timeFrame: 1 year after the last patient is enrolled and 2 years after the last patient is enrolled
measure: Mean change from baseline in the Lym subscale
timeFrame: 1 year after the last patient is enrolled and 2 years after the last patient is enrolled
measure: Mean change from baseline in the EQ-5D-5L index
timeFrame: 1 year after the last patient is enrolled and 2 years after the last patient is enrolled
measure: Mean plasma concentrations of ibrutinib
timeFrame: Up to Cycle 2, Day 21
measure: Maximum observed plasma concentration of ibrutinib
timeFrame: Up to Cycle 2, Day 21
measure: Minimum observed plasma concentration of ibrutinib
timeFrame: Up to Cycle 2, Day 21
measure: Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib
timeFrame: Up to Cycle 2, Day 21
measure: The number of participants affected by an adverse event
timeFrame: Up to 30 days after the last dose of study medication
measure: Overall response rate
timeFrame: 1 year after the last patient is enrolled and 2 years after the last patient is enrolled
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Stanford
country: United States
state: California
city: Norwalk
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Goshen
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Sioux City
country: United States
state: Iowa
city: Westwood
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Metairie
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Jefferson City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Watertown
country: United States
state: South Dakota
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Burlington
country: United States
state: Vermont
city: Charlottesville
country: United States
state: Virginia
city: Morgantown
country: United States
state: West Virginia
city: Madison
country: United States
state: Wisconsin
city: Brugge
country: Belgium
city: Gent
country: Belgium
city: Grenoble
country: France
city: Mulhouse N/A
country: France
city: Nantes
country: France
city: Pessac
country: France
city: Vandoeuvre Les Nancy
country: France
city: Afula
country: Israel
city: Beer Yaakov
country: Israel
city: Hadera
country: Israel
city: Haifa
country: Israel
city: Nahariya
country: Israel
city: Petah Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Chorzow
country: Poland
city: Lodz
country: Poland
city: San Juan
country: Puerto Rico
city: Nizhny Novgorod
country: Russian Federation
city: Rostov-Na-Donu
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: St.-Petersburg
country: Russian Federation
city: Barcelona
country: Spain
city: Salamanca
country: Spain
city: London
country: United Kingdom
city: Plymouth
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: