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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT01599949

Collaborator

Pharmacyclics LLC. (Industry)

120

Enrollment

Locations

Arm

Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma	Drug: Ibrutinib	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2012

Actual Primary Completion Date :

May 1, 2015

Actual Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ibrutinib	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.

Arm

Intervention/Treatment

Experimental: Ibrutinib

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.

Outcome Measures

Primary Outcome Measures

Overall response rate [1 year after the last patient is enrolled]

Secondary Outcome Measures

Overall survival rate [1 year after the last patient is enrolled and 2 years after the last patient is enrolled]
Progression-free survival rate [1 year after the last patient is enrolled and 2 years after the last patient is enrolled]
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]
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]
Mean plasma concentrations of ibrutinib [Up to Cycle 2, Day 21]
Maximum observed plasma concentration of ibrutinib [Up to Cycle 2, Day 21]
Minimum observed plasma concentration of ibrutinib [Up to Cycle 2, Day 21]
Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib [Up to Cycle 2, Day 21]
The number of participants affected by an adverse event [Up to 30 days after the last dose of study medication]
Overall response rate [1 year after the last patient is enrolled and 2 years after the last patient is enrolled]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country
1	La Jolla	California	United States
2	Los Angeles	California	United States
3	Stanford	California	United States
4	Norwalk	Connecticut	United States
5	Jacksonville	Florida	United States
6	Chicago	Illinois	United States
7	Peoria	Illinois	United States
8	Goshen	Indiana	United States
9	Iowa City	Iowa	United States
10	Sioux City	Iowa	United States
11	Westwood	Kansas	United States
12	Lexington	Kentucky	United States
13	Louisville	Kentucky	United States
14	Metairie	Louisiana	United States
15	Baltimore	Maryland	United States
16	Boston	Massachusetts	United States
17	Worcester	Massachusetts	United States
18	Ann Arbor	Michigan	United States
19	Detroit	Michigan	United States
20	Jefferson City	Missouri	United States
21	Saint Louis	Missouri	United States
22	Omaha	Nebraska	United States
23	Hackensack	New Jersey	United States
24	New York	New York	United States
25	Syracuse	New York	United States
26	Watertown	South Dakota	United States
27	Nashville	Tennessee	United States
28	Houston	Texas	United States
29	Burlington	Vermont	United States
30	Charlottesville	Virginia	United States
31	Morgantown	West Virginia	United States
32	Madison	Wisconsin	United States
33	Brugge		Belgium
34	Gent		Belgium
35	Grenoble		France
36	Mulhouse N/A		France
37	Nantes		France
38	Pessac		France
39	Vandoeuvre Les Nancy		France
40	Afula		Israel
41	Beer Yaakov		Israel
42	Hadera		Israel
43	Haifa		Israel
44	Nahariya		Israel
45	Petah Tikva		Israel
46	Ramat Gan		Israel
47	Chorzow		Poland
48	Lodz		Poland
49	San Juan		Puerto Rico
50	Nizhny Novgorod		Russian Federation
51	Rostov-Na-Donu		Russian Federation
52	St-Petersburg		Russian Federation
53	St.-Petersburg		Russian Federation
54	Barcelona		Spain
55	Salamanca		Spain
56	London		United Kingdom
57	Plymouth		United Kingdom