Back to resultsA Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Primary Purpose
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ibrutinib
Bendamustine hydrochloride
Rituximab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Chronic lymphocytic leukemia, Small lymphocytic lymphoma, Relapsed or refractory chronic lymphocytic leukemia, Relapsed or refractory small lymphocytic lymphoma, Ibrutinib, PCI-32765, JNJ-54179060, Bruton's tyrosine kinase inhibitor, Bendamustine, Rituximab
Eligibility 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
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ibrutinib + BR
Placebo + BR
Arm Description
Ibrutinib 420 mg will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with bendamustine and rituximab (BR) for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).
Matching placebo will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with BR for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS)
PFS was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. IWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other new organ infiltrates, bone lesion, ascites, or pleural effusion confirmed due to chronic lymphocytic leukemia (CLL); >=50% increase in existing lymph nodes; >=50% increase in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) or >=50% increase from nadir count confirmed on >=2 serial assessments if absolute lymphocyte count (ALC) >=30,000 per microliter and lymphocyte doubling time is rapid, unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b [Hgb] or platelets) attributable to CLL; and transformation to a more aggressive histology.
Secondary Outcome Measures
Overall Response Rate (ORR)
ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL) and absolute lymphocyte count <4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR-2 of the following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum products of up to 6 lymph nodes, >=50% decrease in enlargement of spleen or liver; and 1 of the following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; no new enlarged nodes or new hepatosplenomegaly.
Overall Survival (OS)
OS was defined as the interval between the date of randomization and the date of death from any cause.
Percentage of Participants With Minimal Residual Disease (MRD)-Negative Response
MRD-negative response was defined as the percentage of participants who reach MRD negative disease status (less than 1 chronic lymphocytic leukemia [CLL] cell per 10,000 leukocytes) in either bone marrow or peripheral blood. All randomized participants were included in this analysis. Participants with missing MRD data were considered non-responders.
Percentage of Participants With Sustained Hematologic Improvement
Sustained hematologic improvement was defined as hematological improvement that was sustained continuously for greater than or equal to (>=) 56 days without blood transfusion or growth factors: 1) Platelet counts greater than (>)100* 109/liter (L) if baseline less than or equal to (<=) 100*109/L or increase >= 50 percent (%) over baseline; 2) Hemoglobin >11 gram per deciliters (g/dL) if baseline <= 11 g/dL or increase >= 2 g/dL over baseline.
Median Time to Clinically Meaningful Improvement in FACIT-Fatigue Scale
Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms
The disease-related symptoms included fatigue, weight loss, fevers, night sweats, abdominal discomfort/splenomegaly and anorexia.
Number of Participants Who Received Subsequent Antineoplastic Therapy
Number of participants who received subsequent antineoplastic therapy was reported.
Change From Baseline in Beta2 Microglobulin at End of Treatment (EOT)
Change from baseline in beta2 microglobulin at end of treatment at time of primary analysis was reported.
Change From Baseline in FACIT-Fatigue Scale at End of Treatment
FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Change From Baseline in EORTC QLQ-C30 Physical Functioning Score at End of Treatment
EORTC QLQ-C30 Physical Functioning Score is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which was rated on a 7-point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening. All scale and item scores were linearly transformed to be in range from 0-100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms.
Change From Baseline in EORTC QLQ-CLL 16 Domain Scores at End of Treatment
The EORTC QLQ-CLL 16 is a 16-item disease specific module that comprises 5 domains of patient-reported health status important in CLL. There are three multi-item scales that include fatigue (2 items), treatment side effects and disease symptoms (8 items), and infection (4 items), and 2 single-item scales on social activities and future health worries. Responses are measured on a 4 point scale ranging from 1 (not at all) to 4 (very much).
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Visual Analog Scale at End of Treatment
The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Utility Score Scale at End of Treatment
The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1. High score indicating a high level of utility.
Full Information
NCT ID
NCT01611090
First Posted
May 15, 2012
Last Updated
February 20, 2020
Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.
1. Study Identification
Unique Protocol Identification Number
NCT01611090
Brief Title
A Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
September 19, 2012 (Actual)
Primary Completion Date
January 23, 2019 (Actual)
Study Completion Date
January 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to examine the safety and efficacy of Ibrutinib administered in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Detailed Description
This is a randomized (patients will be assigned by chance to study treatments), double-blind (patients and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to determine the benefits and risks of combining ibrutinib with bendamustine and rituximab (BR) in patients with relapsed or refractory CLL/SLL following at least 1 line of prior systemic therapy. Approximately 580 patients will be randomized in a 1:1 ratio to either treatment arm A (placebo) or treatment arm B (ibrutinib 420 mg).
Study medication will be administered orally once daily on a continuous schedule. All patients will receive BR as the background therapy plus either ibrutinib or placebo for a maximum of 6 cycles, after which treatment with ibrutinib or placebo will continue until disease progression or unacceptable toxicity.
A treatment cycle will be defined as 28 days. The study will include a screening phase, a treatment phase, and a follow-up phase. Study end is defined as when either 80% of the patients have died or 5 years after the last patient is randomized into the study, whichever occurs first.
Patients in treatment arm A (placebo) who complete the treatment phase, with disease progression or (after interim analysis) meet International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for treatment, may crossover to ibrutinib treatment (as in treatment arm B), at the investigators discretion. This open-label, next-line treatment with ibrutinib will continue until disease progression, unacceptable toxicity, withdrawal from study, or until the study end, whichever occurs earlier. One interim analysis is planned for the study. Efficacy evaluations will include computed tomography scans, laboratory testing, focused physical examinations, bone marrow biopsy and aspirate, and assessment of patient-reported outcomes. In both treatment arms, samples for the development of a population-based pharmacokinetic (PK; study of what the body does to a drug) approach will be collected. Safety will be assessed throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
Chronic lymphocytic leukemia, Small lymphocytic lymphoma, Relapsed or refractory chronic lymphocytic leukemia, Relapsed or refractory small lymphocytic lymphoma, Ibrutinib, PCI-32765, JNJ-54179060, Bruton's tyrosine kinase inhibitor, Bendamustine, Rituximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
578 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ibrutinib + BR
Arm Type
Experimental
Arm Description
Ibrutinib 420 mg will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with bendamustine and rituximab (BR) for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).
Arm Title
Placebo + BR
Arm Type
Placebo Comparator
Arm Description
Matching placebo will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with BR for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Description
Type=exact number, unit=mg, number=420 , form=capsule, route=oral use. Capsule is taken once daily continuously.
Intervention Type
Drug
Intervention Name(s)
Bendamustine hydrochloride
Intervention Description
Type=exact number, unit=mg, number=70 mg/m2, route=intravenous use. Administered intravenously on Cycle 1, Days 2-3 and Cycles 2-6, Days 1-2.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Type=exact number, unit=mg, number=375 mg/m2 and 500 mg/m2, route=intravenous use. Administered intravenously on Cycle 1, Day 1, and Cycles 2-6, Day 1, respectively.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Form=capsule, route=oral use. Capsule is taken once daily continuously.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
PFS was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. IWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other new organ infiltrates, bone lesion, ascites, or pleural effusion confirmed due to chronic lymphocytic leukemia (CLL); >=50% increase in existing lymph nodes; >=50% increase in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) or >=50% increase from nadir count confirmed on >=2 serial assessments if absolute lymphocyte count (ALC) >=30,000 per microliter and lymphocyte doubling time is rapid, unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b [Hgb] or platelets) attributable to CLL; and transformation to a more aggressive histology.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL) and absolute lymphocyte count <4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR-2 of the following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum products of up to 6 lymph nodes, >=50% decrease in enlargement of spleen or liver; and 1 of the following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; no new enlarged nodes or new hepatosplenomegaly.
Time Frame
Up to 5 years
Title
Overall Survival (OS)
Description
OS was defined as the interval between the date of randomization and the date of death from any cause.
Time Frame
Up to 5 years
Title
Percentage of Participants With Minimal Residual Disease (MRD)-Negative Response
Description
MRD-negative response was defined as the percentage of participants who reach MRD negative disease status (less than 1 chronic lymphocytic leukemia [CLL] cell per 10,000 leukocytes) in either bone marrow or peripheral blood. All randomized participants were included in this analysis. Participants with missing MRD data were considered non-responders.
Time Frame
Up to 5 years
Title
Percentage of Participants With Sustained Hematologic Improvement
Description
Sustained hematologic improvement was defined as hematological improvement that was sustained continuously for greater than or equal to (>=) 56 days without blood transfusion or growth factors: 1) Platelet counts greater than (>)100* 109/liter (L) if baseline less than or equal to (<=) 100*109/L or increase >= 50 percent (%) over baseline; 2) Hemoglobin >11 gram per deciliters (g/dL) if baseline <= 11 g/dL or increase >= 2 g/dL over baseline.
Time Frame
Up to 5 years
Title
Median Time to Clinically Meaningful Improvement in FACIT-Fatigue Scale
Description
Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Time Frame
Up to 2 years
Title
Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms
Description
The disease-related symptoms included fatigue, weight loss, fevers, night sweats, abdominal discomfort/splenomegaly and anorexia.
Time Frame
From the date of randomization to disease progression (Up to 2 years)
Title
Number of Participants Who Received Subsequent Antineoplastic Therapy
Description
Number of participants who received subsequent antineoplastic therapy was reported.
Time Frame
Up to 5 years
Title
Change From Baseline in Beta2 Microglobulin at End of Treatment (EOT)
Description
Change from baseline in beta2 microglobulin at end of treatment at time of primary analysis was reported.
Time Frame
Baseline to EOT (Up to 2 years)
Title
Change From Baseline in FACIT-Fatigue Scale at End of Treatment
Description
FACIT-Fatigue is an instrument for use as a measure of the effect of fatigue in patients with cancer and other chronic diseases. Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).
Time Frame
Baseline to EOT (up to 2 years)
Title
Change From Baseline in EORTC QLQ-C30 Physical Functioning Score at End of Treatment
Description
EORTC QLQ-C30 Physical Functioning Score is a questionnaire to assess quality of life of cancer patients. It is composed of 30 items, multi-item measure (28 items) and 2 single-item measures. For the multiple item measure, 4-point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which was rated on a 7-point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening. All scale and item scores were linearly transformed to be in range from 0-100. A higher score represents a higher (better) level of functioning, or a higher (worse) level of symptoms.
Time Frame
Baseline to EOT (up to 2 years)
Title
Change From Baseline in EORTC QLQ-CLL 16 Domain Scores at End of Treatment
Description
The EORTC QLQ-CLL 16 is a 16-item disease specific module that comprises 5 domains of patient-reported health status important in CLL. There are three multi-item scales that include fatigue (2 items), treatment side effects and disease symptoms (8 items), and infection (4 items), and 2 single-item scales on social activities and future health worries. Responses are measured on a 4 point scale ranging from 1 (not at all) to 4 (very much).
Time Frame
Baseline to EOT (up to 2 years)
Title
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Visual Analog Scale at End of Treatment
Description
The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).
Time Frame
Baseline to EOT (up to 2 years)
Title
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Utility Score Scale at End of Treatment
Description
The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1. High score indicating a high level of utility.
Time Frame
Baseline to EOT (up to 2 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Phoenix
State/Province
Arizona
Country
United States
City
Berkeley
State/Province
California
Country
United States
City
Duarte
State/Province
California
Country
United States
City
Greenbrae
State/Province
California
Country
United States
City
Stamford
State/Province
Connecticut
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Boca Raton
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Marietta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Springfield
State/Province
Illinois
Country
United States
City
Fort Wayne
State/Province
Indiana
Country
United States
City
Goshen
State/Province
Indiana
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Iowa City
State/Province
Iowa
Country
United States
City
Westwood
State/Province
Kansas
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Paducah
State/Province
Kentucky
Country
United States
City
Marrero
State/Province
Louisiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Battle Creek
State/Province
Michigan
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Lansing
State/Province
Michigan
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Lincoln
State/Province
Nebraska
Country
United States
City
Lebanon
State/Province
New Hampshire
Country
United States
City
Hackensack
State/Province
New Jersey
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
Dunkirk
State/Province
New York
Country
United States
City
Hawthorne
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Bismarck
State/Province
North Dakota
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Sioux Falls
State/Province
South Dakota
Country
United States
City
Temple
State/Province
Texas
Country
United States
City
Morgantown
State/Province
West Virginia
Country
United States
City
Buenos Aires
Country
Argentina
City
Ciudad Autonoma Buenos Aires
Country
Argentina
City
Ciudad Autonoma de Buenos Aires
Country
Argentina
City
Cordoba
Country
Argentina
City
Aalst
Country
Belgium
City
Brugge
Country
Belgium
City
Brussels
Country
Belgium
City
Gent
Country
Belgium
City
Leuven
Country
Belgium
City
Rio de Janeiro
Country
Brazil
City
Salvador
Country
Brazil
City
Sao Paulo
Country
Brazil
City
Edmonton
State/Province
Alberta
Country
Canada
City
Vancouver N/a
State/Province
British Columbia
Country
Canada
City
Hamilton
State/Province
Ontario
Country
Canada
City
London
State/Province
Ontario
Country
Canada
City
Ottawa
State/Province
Ontario
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
Bogota
Country
Colombia
City
Floridablanca
Country
Colombia
City
Brno
Country
Czechia
City
Praha 10
Country
Czechia
City
Praha 2
Country
Czechia
City
Creteil
Country
France
City
Montpellier
Country
France
City
Paris Cedex 13
Country
France
City
Pessac
Country
France
City
Pierre Benite
Country
France
City
Tours
Country
France
City
Villejuif
Country
France
City
Aschaffenburg
Country
Germany
City
Augsburg
Country
Germany
City
Dresden
Country
Germany
City
Erlangen
Country
Germany
City
Essen
Country
Germany
City
Frankfurt
Country
Germany
City
Frechen
Country
Germany
City
Hamm
Country
Germany
City
Heidelberg
Country
Germany
City
Homburg/Saar
Country
Germany
City
Kassel
Country
Germany
City
Kiel
Country
Germany
City
Koblenz
Country
Germany
City
Köln
Country
Germany
City
Kÿln N/a
Country
Germany
City
Lebach
Country
Germany
City
Magdeburg
Country
Germany
City
Mannheim
Country
Germany
City
Marburg
Country
Germany
City
Mutlangen
Country
Germany
City
Ulm
Country
Germany
City
Würzburg
Country
Germany
City
Athens
Country
Greece
City
Thessalonikis
Country
Greece
City
Haifa
Country
Israel
City
Jerusalem
Country
Israel
City
Nahariya
Country
Israel
City
Netanya
Country
Israel
City
Petah Tikva
Country
Israel
City
Ramat-Gan
Country
Israel
City
Tel Aviv
Country
Israel
City
Seoul
Country
Korea, Republic of
City
Mexico
Country
Mexico
City
Monterrey
Country
Mexico
City
Oaxaca
Country
Mexico
City
Brzozow
Country
Poland
City
Chorzów
Country
Poland
City
Krakow
Country
Poland
City
Opole
Country
Poland
City
Slupsk
Country
Poland
City
Coimbra
Country
Portugal
City
Lisboa
Country
Portugal
City
Ponta Delgada
Country
Portugal
City
Porto
Country
Portugal
City
Arkhangelsk
Country
Russian Federation
City
Dzerzhinsk
Country
Russian Federation
City
Ekaterinburg
Country
Russian Federation
City
Krasnodar
Country
Russian Federation
City
Moscow N/a
Country
Russian Federation
City
Moscow
Country
Russian Federation
City
Nizhniy Novgorod
Country
Russian Federation
City
Obninsk
Country
Russian Federation
City
Perm
Country
Russian Federation
City
Rostov-Na-Donu
Country
Russian Federation
City
Ryazan
Country
Russian Federation
City
Saint Petersburg
Country
Russian Federation
City
Samara
Country
Russian Federation
City
Sochi
Country
Russian Federation
City
St. Petersburg
Country
Russian Federation
City
St.-Petersburg
Country
Russian Federation
City
Syktyvkar
Country
Russian Federation
City
Barcelona
Country
Spain
City
L'hospitalet De Llobregat
Country
Spain
City
Madrid
Country
Spain
City
Salamanca
Country
Spain
City
Valencia
Country
Spain
City
Göteborg
Country
Sweden
City
Huddinge
Country
Sweden
City
Stockholm
Country
Sweden
City
UMEå
Country
Sweden
City
Ankara
Country
Turkey
City
Istanbul
Country
Turkey
City
Izmir
Country
Turkey
City
Kayseri
Country
Turkey
City
Cherkassy
Country
Ukraine
City
Dnepropetrovsk
Country
Ukraine
City
Donetsk
Country
Ukraine
City
Khakhiv
Country
Ukraine
City
Khmelnitskiy
Country
Ukraine
City
Kiev
Country
Ukraine
City
Lviv
Country
Ukraine
City
Vinnitsa
Country
Ukraine
City
Birmingham
Country
United Kingdom
City
Harrow
Country
United Kingdom
City
Plymouth
Country
United Kingdom
City
Sheffield Yorks
Country
United Kingdom
City
Sutton
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32762271
Citation
Fraser GAM, Chanan-Khan A, Demirkan F, Santucci Silva R, Grosicki S, Janssens A, Mayer J, Bartlett NL, Dilhuydy MS, Loscertales J, Avigdor A, Rule S, Samoilova O, Pavlovsky MA, Goy A, Mato A, Hallek M, Salman M, Tamegnon M, Sun S, Connor A, Nottage K, Schuier N, Balasubramanian S, Howes A, Cramer P. Final 5-year findings from the phase 3 HELIOS study of ibrutinib plus bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Leuk Lymphoma. 2020 Dec;61(13):3188-3197. doi: 10.1080/10428194.2020.1795159. Epub 2020 Aug 6.
Results Reference
derived
PubMed Identifier
31044267
Citation
Lavezzi SM, de Jong J, Neyens M, Cramer P, Demirkan F, Fraser G, Bartlett N, Dilhuydy MS, Loscertales J, Avigdor A, Rule S, Samoilova O, Goy A, Ganguly S, Salman M, Howes A, Mahler M, De Nicolao G, Poggesi I. Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial. Pharm Res. 2019 May 1;36(7):93. doi: 10.1007/s11095-019-2605-8.
Results Reference
derived
PubMed Identifier
28751558
Citation
Brown JR, Moslehi J, O'Brien S, Ghia P, Hillmen P, Cymbalista F, Shanafelt TD, Fraser G, Rule S, Kipps TJ, Coutre S, Dilhuydy MS, Cramer P, Tedeschi A, Jaeger U, Dreyling M, Byrd JC, Howes A, Todd M, Vermeulen J, James DF, Clow F, Styles L, Valentino R, Wildgust M, Mahler M, Burger JA. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica. 2017 Oct;102(10):1796-1805. doi: 10.3324/haematol.2017.171041. Epub 2017 Jul 27.
Results Reference
derived
PubMed Identifier
26655421
Citation
Chanan-Khan A, Cramer P, Demirkan F, Fraser G, Silva RS, Grosicki S, Pristupa A, Janssens A, Mayer J, Bartlett NL, Dilhuydy MS, Pylypenko H, Loscertales J, Avigdor A, Rule S, Villa D, Samoilova O, Panagiotidis P, Goy A, Mato A, Pavlovsky MA, Karlsson C, Mahler M, Salman M, Sun S, Phelps C, Balasubramanian S, Howes A, Hallek M; HELIOS investigators. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016 Feb;17(2):200-211. doi: 10.1016/S1470-2045(15)00465-9. Epub 2015 Dec 5.
Results Reference
derived
Learn more about this trial
A Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
We'll reach out to this number within 24 hrs