Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pharmacyclics
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01646021
First received: July 18, 2012
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus temsirolimus in patients with relapsed or refractory mantle cell lymphoma who received at least 1 prior chemotherapy regimen.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Ibrutinib
Drug: Temsirolimus
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression free survival [ Time Frame: clinical cutoff (defined by 178 patients with progression free survival events; up to 3 years after the last patient is randomized) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • 1-year survival rate [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Time-to-next treatment [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Mean plasma concentrations of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  • Minimum observed plasma concentration of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib [ Time Frame: Cycles 1-2: predose on Day 1, postdose at 1, 2, and 4 hours; and Cycle 3: predose on Day 1 ] [ Designated as safety issue: No ]
  • Mean change from baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale score [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Mean change from baseline in EuroQol (EQ-5D-5L) index score [ Time Frame: up to 3 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Mean change from baseline in medical resource utilization [ Time Frame: up to 30 days from last dose of study medication ] [ Designated as safety issue: No ]
  • Mean change from baseline in biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways [ Time Frame: up to 30 days from last dose of study medication ] [ Designated as safety issue: No ]
  • Mean change from baseline in identified resistance biomarkers from bone marrow [ Time Frame: up to 30 days from last dose of study medication ] [ Designated as safety issue: No ]

Enrollment: 280
Study Start Date: December 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ibrutinib Drug: Ibrutinib
560 mg once daily continuous (without interruption) by mouth for 21-day cycles
Experimental: Temsirolimus Drug: Temsirolimus
175 mg once daily intravenous infusion on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each 21-day cycle

Detailed Description:

This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known), study to evaluate the efficacy and safety of ibrutinib when compared with temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 1 prior rituximab-containing chemotherapy regimen. Approximately 280 eligible patients will be randomly assigned in a 1:1 ratio and stratified (grouped) by the number of prior lines of therapy (1 or 2 versus >=3) and simplified MCL International Prognostic Index criteria to receive either ibrutinib by mouth (Treatment Arm A) or temsirolimus intravenous infusion (Treatment Arm B). The study will consist of screening, treatment, and posttreatment phases. Data will be collected on disease response to the treatment, progression-free survival, overall survival, subsequent anti-MCL therapies, patient reported outcomes, and medical resource utilization. Tumor samples, blood collected at multiple time points, and a bone marrow aspirate will be evaluated to identify markers predictive of response or resistance to ibrutinib. 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. Disease evaluations will be performed every 9 weeks for up to 15 months from the start of study drug, and every 24 weeks thereafter, until disease progression, death, or the clinical cutoff, whichever comes first. Patients who receive treatment with temsirolimus and have disease progression (confirmed by an Independent Review Committee) may be eligible to crossover and receive treatment with ibrutinib 560 mg orally, daily, on a 21-day cycle until disease progression, unacceptable toxicity, or study end. Data will be analyzed up to 3 years after the 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:

  • Confirmed diagnosis of mantle cell lymphoma (MCL)
  • Received at least 1 prior rituximab-containing chemotherapy regimen (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)
  • Documented relapse or disease progression following the last anti-MCL treatment
  • At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
  • Eastern Cooperative Oncology Group performance status grade 0 or 1
  • Protocol-defined hematology and biochemistry laboratory values

Exclusion Criteria:

  • Prior nitrosoureas within 6 weeks, chemotherapy within 3 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 randomization
  • Prior treatment with temsirolimus, other mTOR inhibitors, ibrutinib, or other Bruton's tyrosine kinase (BTK) inhibitors
  • Known central nervous system lymphoma
  • Received an allogeneic or autologous hematopoietic stem cell transplant <=6 months from the date of randomization and on immunosuppressive therapy or have evidence of active graft versus host disease
  • 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 randomization, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease
  • History of stroke or intracranial hemorrhage within 6 months prior to randomization
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonist
  • Requires treatment with strong CYP3A inhibitor
  • 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 (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection or any uncontrolled active systemic infection requiring intravenous antibiotics
  • Woman who is pregnant or breast-feeding
  • 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: NCT01646021

  Show 97 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: NCT01646021     History of Changes
Other Study ID Numbers: CR100848, PCI-32765MCL3001, 2012-000601-74, U1111-1135-6930
Study First Received: July 18, 2012
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Portugal: National Pharmacy and Medicines Institute
Germany: Ethics Commission

Keywords provided by Janssen Research & Development, LLC:
Mantle cell lymphoma
Relapsed mantle cell lymphoma
Refractory mantle cell lymphoma
Ibrutinib
Bruton's tyrosine kinase inhibitor
Temsirolimus

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
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014