A Study of Ibrutinib in Combination with Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.

• Register: EUCTR
• Last refreshed on: 8 January 2018
• Main ID: EUCTR2012-000600-15-DE
• Date of registration: 16/07/2012
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: A Study of Ibrutinib in Combination with Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.
• Scientific title: Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination with Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
• Date of first enrolment: 30/04/2013
• Target sample size: 580
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000600-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes 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

Argentina, Belgium, Brazil, Canada, Colombia, Czech Republic, France, Germany, Greece, Israel, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

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:
•Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
•Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment
•Measurable nodal disease by computed tomography
•Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen
•Eastern Cooperative Oncology Group Performance Status score of 0 or 1
•Hematology and biochemical values within protocol defined limits
•Agrees to protocol-defined use of effective contraception
•Women of childbearing potential must have negative blood or urine pregnancy test at screening

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 174
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 406

Exclusion criteria:
•Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy)
•Prior treatment with ibrutinib or other Bruton’s tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib
•The presence of deletion of the short arm of chromosome 17
•Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen
•Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
•Received a hematopoietic stem cell transplant
•Known central nervous system leukemia/lymphoma or Richter’s transformation
•Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
•Chronic use of corticosteroids
•History of prior malignancy, 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; or clinically significant cardiovascular disease
•Requires anticoagulation with warfarin or equivalent vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors
•Known history of human immunodeficiency virus or hepatitis C, or active infection with hepatitis B or C
•Any uncontrolled active systemic infection or 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
•A woman who is pregnant or breast feeding, or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug



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

Health Condition(s) or Problem(s) studied

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864

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

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 milligram(s)
Concentration type: equal
Concentration number: 140-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 5 years after the last patient is randomized

Main Objective: The primary objective is to determine whether the addition of ibrutinib to BR significantly improves PFS compared with BR in subjects with relapsed or refractory CLL/SLL.

Primary end point(s): Progression-free survival

Secondary Objective: The secondary objectives are:
? To evaluate the safety of ibrutinib in combination with BR
? To evaluate the ORR
? To evaluate the OS
? To evaluate the rate of MRD-negative remissions
? To evaluate improvement in hematologic parameters
? To evaluate improvement of disease-related symptoms
? To evaluate patient-reported symptoms, functional status, and well-being as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30, EORTC QLQ-CLL 16, EQ-5D-5L, and Functional Assessm. of Chronic Illness Therapy (FACIT)-Fatigue Scale
? To characterize the PK of ibrutinib and explore potential effect on BR PK, the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information
? To examine biomarkers related to BCR and compensatory signaling pathways and explore their association with resistance to ibrutinib treatment

Secondary Outcome(s)

Secondary end point(s): 1/ Number of participants with adverse events
2/ Overall response rate
3/ Overall survival
4/ Rate of minimal residual disease (MRD)-negative remissions
5/ Number of participants with improvement in hematologic values
6/ Number of participants with improvement in disease-related symptoms
7/ Number of participants with improvement in patient reported
outcome scores
8/ Plasma concentrations of ibrutinib
9/ Plasma concentrations of bendamustine
10/ Plasma concentrations of rituximab
11/ Number of participants with biomarkers related to B-cell receptors

Timepoint(s) of evaluation of this end point: 1/ Up to 30 days following the last dose of study drug
2/ At disease progression, up to 5 years after the last patient is randomized
3/ Up to 5 years after the last patient is randomized
4-7/ Up to disease progression, up to 5 years after the last patient is randomized
8-9/ Up to Day 2, Cycle 6
10/ Up to Day 1, Cycle 12
11/ End-of-treatment visit (up to Day 450)

Secondary ID(s)

PCI-32765CLL3001

2012-000600-15-SE

Source(s) of Monetary Support

Janssen Research & Development, LLC