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: 11 December 2017
• Main ID: EUCTR2012-000601-74-PT
• Date of registration: 29/08/2012
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• 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 - NAP
• Date of first enrolment: 09/11/2012
• 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: yes Other specify the comparator: Temsirolimus 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, Colombia, Czech Republic, France, Germany, Hungary, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Russian Federation, Spain, Sweden, Taiwan, 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:
- 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 biochemical laboratory values
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 84
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 196

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 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

Relapsed or refractory Mantle Cell Lymphoma
MedDRA version: 19.1 Level: PT Classification code 10026801 Term: Mantle cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Trade Name: IMBRUVICA®
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 milligram(s)
Concentration type: equal
Concentration number: 140-

Trade Name: Torisel
Product Name: Temsirolimus
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: TEMSIROLIMUS
CAS Number: 162635-04-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Secondary Objective: The secondary objectives are:
•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)

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 rituximab-containing chemotherapy regimen.

Primary end point(s): Progression free survival

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 last patient randomized
-up to 3 years after last patient randomized
-Month 12
-up to 3 years after last patient randomized
-up to 3 years after last patient randomized
-up to 30 days after last dose of study medication
-Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
-Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
-Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
-Cycles 1-3: predose on Day 1, Cycles 1-2: postdose at 1, 2, and 4 hours
-up to 3 years after last patient randomized
-up to 3 years after last patient 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 Research & Development, LLC