Back to resultsStudy of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
Primary Purpose
Follicular Lymphoma, B-cell Lymphoma, Non-Hodgkin's Lymphoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ibrutinib
rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma focused on measuring Pharmacyclics (PCYC), PCYC, Lymphoma, Follicular Lymphoma, FL, Rituximab, Ibrutinib, Rituxan, Non-Hodgkin's Lymphoma (NHL), NHL, B-cell Lymphoma
Eligibility Criteria
Key Inclusion criteria:
- Histologically documented FL (Grade 1, 2 and 3A)
- Not previously treated with prior anti-cancer therapy for FL
- Stage II, III or IV disease
- At least one measurable lesion ≥ 2 cm in longest diameter by CT and/or MRI scan
- Men and women ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Key Exclusion criteria:
- Medically apparent central nervous system lymphoma or leptomeningeal disease
- FL with evidence of large cell transformation
- Any prior history of other hematologic malignancy besides FL or myelodysplasia
History of other malignancies, except
- Malignancy treated with curative intent and with no known active disease present for ≥5 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Currently active, clinically significant cardiovascular disease or myocardial infarction within 6 months of screening
- Known anaphylaxis or Immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab (Rituxan®)
- Requires anti-coagulation with warfarin or a vitamin K antagonist.
- Requires treatment with strong cytochrome P450 (CYP) 3A inhibitors.
- Known bleeding diathesis or hemophilia
Sites / Locations
- Providence Saint Joseph Medical Center
- City of Hope
- UCLA Medical Center
- Stanford University, Stanford Care Center
- Southeastern Regional Medical Center
- Community Health Network Community Regional Cancer Center North
- Comprehensive Cancer Centers of Nevada
- Memorial Sloan-Kettering Cancer Center
- Weill Cornell Medical College New York-Presbyterian Hospital
- Mid-Ohio Oncology/ Hematology Inc
- Tennessee Oncology, PLLC The Sarah Cannon Research Institute
- The University of Texas MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Main Study Arm 1
Exploratory Study Arm 2
Arm Description
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR)
Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as >=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses.
Secondary Outcome Measures
Duration of Response (DOR)
DOR is defined as the interval between the date of the first documented response (CR, PR) and the date of the first documented evidence of progressive disease (PD) or death. DOR will be analyzed for the subjects who achieve an overall response during the duration of study.
Progression Free Survival (PFS)
PFS is defined as the time interval between the date of the first dose and the date of the earliest occurrence of PD or death due to any cause, whichever occurs first. PD is characterized by any new lesion or increase by >=50% of previously involved sites from nadir.
Overall Survival (OS)
Subjects will be followed for survival information up to three years after the last dose of study treatment, until new treatment or death, whichever occurs first. OS is defined as the duration of time from the date of the first dose to the date of death from any cause.
Number of Participants With Treatment-emergent Adverse Events
Frequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01980654
Brief Title
Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
Official Title
A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open-label, Phase 2 study designed to assess the efficacy and safety of ibrutinib combined with rituximab in previously untreated subjects with Follicular Lymphoma (FL).
Detailed Description
This is an open-label, Phase 2 study designed to assess the efficacy and safety of ibrutinib combined with rituximab in previously untreated subjects with FL.
There are two study treatment arms.
Subjects enrolled into main study treatment arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Subjects enrolled into the exploratory study treatment arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma, B-cell Lymphoma, Non-Hodgkin's Lymphoma
Keywords
Pharmacyclics (PCYC), PCYC, Lymphoma, Follicular Lymphoma, FL, Rituximab, Ibrutinib, Rituxan, Non-Hodgkin's Lymphoma (NHL), NHL, B-cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Main Study Arm 1
Arm Type
Experimental
Arm Description
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Arm Title
Exploratory Study Arm 2
Arm Type
Experimental
Arm Description
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
PCI-32765
Intervention Description
All subjects will receive 560 mg of Ibrutinib orally.
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
All subjects will receive rituximab 375 mg/m2 intravenously
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR)
Description
Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as >=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses.
Time Frame
Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks.
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
DOR is defined as the interval between the date of the first documented response (CR, PR) and the date of the first documented evidence of progressive disease (PD) or death. DOR will be analyzed for the subjects who achieve an overall response during the duration of study.
Time Frame
Up to 45 months
Title
Progression Free Survival (PFS)
Description
PFS is defined as the time interval between the date of the first dose and the date of the earliest occurrence of PD or death due to any cause, whichever occurs first. PD is characterized by any new lesion or increase by >=50% of previously involved sites from nadir.
Time Frame
Up to 45 months
Title
Overall Survival (OS)
Description
Subjects will be followed for survival information up to three years after the last dose of study treatment, until new treatment or death, whichever occurs first. OS is defined as the duration of time from the date of the first dose to the date of death from any cause.
Time Frame
Up to 45 months
Title
Number of Participants With Treatment-emergent Adverse Events
Description
Frequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions
Time Frame
Up to 45 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion criteria:
Histologically documented FL (Grade 1, 2 and 3A)
Not previously treated with prior anti-cancer therapy for FL
Stage II, III or IV disease
At least one measurable lesion ≥ 2 cm in longest diameter by CT and/or MRI scan
Men and women ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Key Exclusion criteria:
Medically apparent central nervous system lymphoma or leptomeningeal disease
FL with evidence of large cell transformation
Any prior history of other hematologic malignancy besides FL or myelodysplasia
History of other malignancies, except
Malignancy treated with curative intent and with no known active disease present for ≥5 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease.
Adequately treated carcinoma in situ without evidence of disease.
Currently active, clinically significant cardiovascular disease or myocardial infarction within 6 months of screening
Known anaphylaxis or Immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab (Rituxan®)
Requires anti-coagulation with warfarin or a vitamin K antagonist.
Requires treatment with strong cytochrome P450 (CYP) 3A inhibitors.
Known bleeding diathesis or hemophilia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jutta K. Neuenburg, MD, PhD
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Providence Saint Joseph Medical Center
City
Burbank
State/Province
California
ZIP/Postal Code
91505
Country
United States
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University, Stanford Care Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Southeastern Regional Medical Center
City
Newnan
State/Province
Georgia
ZIP/Postal Code
30265
Country
United States
Facility Name
Community Health Network Community Regional Cancer Center North
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89074
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill Cornell Medical College New York-Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Mid-Ohio Oncology/ Hematology Inc
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43219
Country
United States
Facility Name
Tennessee Oncology, PLLC The Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
We'll reach out to this number within 24 hrs