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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pharmacyclics
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01599949
First received: May 14, 2012
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Mantle Cell Lymphoma
Drug: Ibrutinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 1 year after the last patient is enrolled ] [ Designated as safety issue: No ]

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

Enrollment: 120
Study Start Date: August 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01599949

  Show 58 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Pharmacyclics
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01599949     History of Changes
Other Study ID Numbers: CR100847, PCI-32765MCL2001, 2012-000711-88
Study First Received: May 14, 2012
Last Updated: May 9, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Janssen Research & Development, LLC:
Mantle cell lymphoma
Ibrutinib
Bruton's tyrosine kinase inhibitor
Rituximab
Bortezomib

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014