A 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

• Register: EUCTR
• Last refreshed on: 31 January 2017
• Main ID: EUCTR2012-000601-74-IT
• Date of registration: 11/12/2012
• Prospective Registration: Yes
• Primary sponsor: JANSSEN-CILAG INTERNATIONAL N.V.
• Public title: A 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
• Scientific 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
• Date of first enrolment: 08/03/2013
• Target sample size: 280
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000601-74
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Germany, Hungary, Ireland, Italy, Korea, Democratic People's Republic of, Mexico, Netherlands, Portugal, Russian Federation, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
1. 18 years of age or older. 2. Diagnosis of MCL reviewed and approved by central pathology laboratory prior to randomization - diagnosis report from local laboratory must include morphology and expression of either cyclin D1 in association with one B-cell marker (eg, CD19, CD20, or PAX5) and CD5 or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR) - if report from local laboratory is not available, diagnosis must be confirmed by central pathology laboratory based on the criteria above 3. 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. 4. Documented relapse or disease progression following the last anti-MCL treatment. 5. At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma. The site of disease must be greater than 1.5 cm in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions. 6. Eastern Cooperative Oncology Group performance status grade 0 or 1 7. Hematology values must be within the following limits within 7 days prior to randomization: a. Absolute neutrophil count (ANC) = 1000/mm3 independent of growth factor support. b. Platelets = 75,000/mm3 or = 50,000/mm3 if bone marrow involvement independent of transfusion support. c. Hemoglobin level = 8 g/dL independent of transfusion support. 8. Biochemical values within the following limits within 7 days prior to randomization: a.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x upper limit of normal (ULN) b.Total bilirubin = 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin. c. Serum creatinine = 2 x ULN JNJ 54179060 d. Fasting serum cholesterol level = 350 mg/dL e. Fasting serum triglyceride level = 400 mg/dL 9. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study (3 months for both men and women) consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during the study and for 3 months after receiving the last dose of study drug. 10.Women of childbearing potential must have a negative serum (ß-human chorionic gonadotropin [ß-hCG]) or urine pregnancy test at Screening. 11. Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion criteria:
- Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxinimmunoconjugates 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 - Requires treatment with strong CYP3A4/5 or CYP2D6 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 (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 subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Relapsed or refractory Mantle Cell Lymphoma
MedDRA version: 14.1 Level: LLT Classification code 10026808 Term: Mantle zone lymphoma refractory System Organ Class: 100000004864
MedDRA version: 14.1 Level: LLT Classification code 10026807 Term: Mantle zone lymphoma recurrent System Organ Class: 100000004864
MedDRA version: 14.1 Level: LLT Classification code 10026806 Term: Mantle zone lymphoma System Organ Class: 100000004864

Intervention(s)

Product Name: Ibrutinib
Product Code: JNJ-54179060
Pharmaceutical Form: Capsule
INN or Proposed INN: IBRUTINIB
CAS Number: 936563-96-1
Current Sponsor code: JNJ-54179060
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 140-

Trade Name: TORISEL*EV 1FL 30MG+1FL 1,8ML
Pharmaceutical Form: Solution for infusion
CAS Number: 162635-04-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Secondary Objective: •To evaluate the overall response rate (CR + PR) •To evaluate overall survival •To evaluate the 1-year survival rate •To evaluate duration of response •To evaluate time-to-next treatment (TTNT) •To evaluate the safety of ibrutinib and temsirolimus •To characterize the pharmacokinetics of ibrutinib •To evaluate patient-reported outcomes (PRO) utilizing the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and EuroQol (EQ- 5D) •To evaluate medical resource utilization (MRU) information •To identify biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways and to explore their association with response to ibrutinib •To explore the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information.

Timepoint(s) of evaluation of this end point: clinical cutoff (defined by 178 patients with progression free survival events; up to 3 years after the last patient is randomized)

Primary end point(s): Progression free survival

Main Objective: The primary objective of the study is to evaluate whether treatment with ibrutinib compared with temsirolimus will result in prolongation of PFS, as determined by blinded independent central review, in subjects with relapsed or refractory MCL who have received at least 1 prior rituximabcontaining chemotherapy regimen.

Secondary Outcome(s)

Secondary end point(s): - Overall response rate - Overall survival - 1-year survival rate - Duration of response - Time-to-next treatment - Number of participants with adverse events - Mean plasma concentrations of ibrutinib - Maximum observed plasma concentration of ibrutinib - Minimum observed plasma concentration of ibrutinib - Area under the plasma concentration-time curve from time 0 to 24 hours of ibrutinib - Mean change from baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale score - Mean change from baseline in EuroQol (EQ-5D-5L) index score - Mean change from baseline in medical resource utilization - Mean change from baseline in biomarkers that alter B-cell receptor (BCR) signaling or activate alternative signaling pathways - Mean change from baseline in identified resistance biomarkers from bone marrow

Timepoint(s) of evaluation of this end point: -up to 3 years after the last pt is randomized - up to 3 years after the last pt is randomized - Month 12 - up to 3 years after the last pt is randomized - up to 3 years after the last pt is randomized - up to 30 days after the last dose of study medication - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - Cycles 1-3: predose on Day 1; postdose at 1, 2, and 4 hours - up to 3 years after the last pt is randomized - up to 3 years after the last pt is randomized - up to 30 days from last dose of study medication - up to 30 days from last dose of study medication - up to 30 days from last dose of study medication

Secondary ID(s)

PCI-32765MCL3001

2012-000601-74-SE

Source(s) of Monetary Support

JANSSEN CILAG SPA