Follicular Lymphoma
Conditions
Keywords
PCYC, Pharmacyclics, ibrutinib, rituximab, FL, Non-Hodgkin's Lymphoma, NHL
Brief summary
This is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study to evaluate the efficacy and safety of ibrutinib in combination with rituximab versus placebo in combination with rituximab in treatment naïve participants with follicular lymphoma (FL).
Interventions
DRUGIbrutinib Oral Capsule
Ibrutinib 560mg administered orally daily
DRUGPlacebo
Placebo capsules to match ibrutinib administered orally daily
DRUGRituximab
Rituximab 375mg/m\^2 intravenously (IV) weekly
Sponsors
Pharmacyclics LLC.
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of follicular lymphoma CD20+ (Grade 1, 2 or 3a) Ann Arbor Stage II, III or IV disease. * Measurable disease * Subjects 70 years of age or older; OR subjects 60-69 years of age who have one or more comorbidities. * Meets one or more Groupe d'Etude des Lymphomes Folliculaire (GELF) criteria. * Adequate hematologic function within protocol-defined parameters. * Adequate hepatic and renal function within protocol-defined parameters. * ECOG performance status score of 0-2.
Exclusion criteria
* Transformed lymphoma * Prior treatment for follicular lymphoma. * Central nervous system lymphoma or leptomeningeal disease. * Currently active, clinically significant cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as Assessed by Investigator | Primary Analysis cut-off; median overall follow-up of 53.75 months | PFS is the time from the date of randomization to the date of the first documented evidence of disease progression (based on the Revised Response Criteria for Malignant Lymphoma \[Cheson 2014, Lugano Classification\]) or death from any cause, whichever occurs first. Participants who initiated subsequent anticancer therapy or missed two or more consecutive overall disease assessments were censored as described in the SAP. Estimated by Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) as Assessed by Investigator | Primary Analysis; median overall follow-up of 53.75 months | ORR is the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR) as determined by the investigator according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2014, Lugano Classification). ORR was assessed from the date of randomization through the date of first documented disease progression or initiation of subsequent anti-cancer therapy, whichever occurred first. Participants who did not have any post-baseline disease assessments or who initiated subsequent anti-cancer therapy prior to a documented response are considered non-responders. |
| Overall Survival (OS) | Final Analysis; median overall follow-up of 58.97 months | Overall survival is defined as the interval between the date of randomization and the date of the participant's death from any cause. If a participant is not known to have died (this includes participants with unknown death date), OS will be censored at the date the participant was last known to have been alive. Estimated by Kaplan-Meier method. |
| Infusion-related Reaction Rate Assessed by Investigator | Primary Analysis; median overall follow-up of 53.75 months | The infusion-related reactions (IRR) rate is the proportion of subjects experiencing infusion related reactions that start on the day of a rituximab infusion and are assessed as related or possibly related to rituximab. |
| Duration of Response (DOR) as Assessed by Investigator | Primary Analysis; median overall follow-up of 53.75 months | DOR is defined as the time from initial complete response (CR) or partial response (PR) to progressive disease (PD) or death due to any cause, whichever is first reported, regardless of discontinuation of study treatment. If such event did not occur, then participants were to be censored at the last adequate disease assessment as required for PFS censoring. Estimated by Kaplan-Meier method. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Overall median treatment duration of 22.11 months | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The treatment-emergent period is defined as the period from the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment or the day before initiation of subsequent anti-cancer therapy, whichever comes first. The treatment-emergent adverse events (TEAEs) are those events that occur or worsen during the treatment-emergent period or that are related to the study treatment. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Greece, Hungary, Israel, Italy, Netherlands, Poland, Portugal, Russia, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
In total, 445 participants were enrolled at 128 sites in 19 countries. Participants were randomly assigned in a 3:1 ratio to the Ibrutinib + Rituximab arm (Arm A; n=334) or the Placebo + Rituximab arm (Arm B; n=111). Randomization was stratified on the basis of: (a) age (60-69 vs. ≥70 years), (b) Follicular Lymphoma-specific International Prognostic Index (FLIPI)-1 score (low vs. intermediate/high) and (c) ECOG performance status score (0/1 vs. 2).
Pre-assignment details
The intent-to-treat (ITT) population included all randomized participants. The ITT population was the primary population for all efficacy analyses (N=445). The safety population included all participants who received at least one dose of study treatment (N=441).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 74.2 Years STANDARD_DEVIATION 5.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 304 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 401 Participants |
| Sex: Female, Male Female | 236 Participants |
| Sex: Female, Male Male | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 123 / 334 | 40 / 111 |
| other Total, other adverse events | 310 / 334 | 101 / 111 |
| serious Total, serious adverse events | 214 / 334 | 48 / 111 |
Outcome results
None listed