Follicular Lymphoma
Conditions
Keywords
Phase 3, Follicular Lymphoma, FL, PI3K
Brief summary
A study to evaluate the safety and efficacy of duvelisib administered in combination with rituximab vs placebo in combination with rituximab in patients with previously treated CD20-positive follicular lymphoma who are not suitable candidates for chemotherapy.
Detailed description
Study IPI-145-08 is an international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study designed to evaluate the efficacy and safety of duvelisib in combination with rituximab vs placebo in combination with rituximab in subjects with previously treated CD20-positive follicular lymphoma. Approximately 400 subjects will receive 25 mg of duvelisib or placebo, orally BID for 28 day continuous cycles, in combination with 375 mg/m2 of Rituximab given once weekly for 4 weeks during Cycle 1 and then once on Day 1 of Cycles 4, 6, 8, and 10. Patients will remain on treatment for up to 27 cycles and may continue treatment if clinical benefit is observed.
Interventions
DRUGPlacebo
Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles.
DRUGDuvelisib
PI3K Inhibitor
DRUGRituximab
IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
Sponsors
SecuraBio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CD20-positive FL: * Histology grades 1, 2 or 3a * Biopsy-confirmed histopathological diagnosis of FL. Biopsy specimen should be obtained ≤2 years prior to randomization, unless medically contraindicated * CD20 immunophenotyping performed ≤2 years prior to randomization * First or subsequent relapse following at least one induction therapy regimen containing rituximab in combination with an anthracycline or rituximab in combination with an alkylating agent * Patients in first relapse must be chemoresistant or intolerant to chemotherapy * No response or disease progression ≤ 24 months from start of last previous therapy * At least 1 measurable disease lesion \>1.5 cm in at least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression
Exclusion criteria
* Clinical evidence of other indolent forms of lymphoma (e.g., marginal zone lymphoma \[MZL\], small lymphocytic lymphoma \[SLL\]) * Transformation to a more aggressive subtype of lymphoma or grade 3b FL * Refractory to rituximab: defined as disease progression while receiving or within 6 months of completing either weekly rituximab induction therapy, or rituximab-based chemoimmunotherapy induction * Intolerance to rituximab or severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies * Prior allogeneic hematopoietic stem cell transplant (HSCT) * Known Central Nervous System (CNS) lymphoma; subjects with symptoms of CNS disease must have a negative CT scan and negative diagnostic lumbar puncture * Prior treatment with a PI3K inhibitor or BTK inhibitor * History of tuberculosis within the preceding two years * Ongoing systemic bacterial, fungal, or viral infections at randomization (defined as requiring IV antimicrobial, antifungal or antiviral agents) * Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other I/E criteria are met * Prior, current, or chronic hepatitis B or hepatitis C infection, positive result for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) or hepatitis C virus antibodies (HCV Ab) * History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Until disease progression, for up to 5 years from randomization | Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed. |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) | Until disease progression, for up to 5 years from randomization |
Countries
Australia, France, Italy, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duvelisib + Rituximab Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.
Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles
Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | 6 |
| Placebo + Rituximab Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules.
Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg.
Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles.
Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Adverse Event and Investigator decision | 1 | 0 |
| Overall Study | Patient ineligible-medical monitor | 1 | 0 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol-Specified Disease Progression | 0 | 4 |
| Overall Study | Termination of Study bySponsor | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo + Rituximab | Total | Duvelisib + Rituximab |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 7 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 6 Participants | 4 Participants |
| Age, Continuous | 68 years | 68 years | 56.5 years |
| Eastern Cooperative Oncology Group Performance Status 0=Fully active, no restrictions | 6 Participants | 10 Participants | 4 Participants |
| Eastern Cooperative Oncology Group Performance Status 1= Restricted in physically strenuous activity | 1 Participants | 3 Participants | 2 Participants |
| Eastern Cooperative Oncology Group Performance Status 2=Ambulatory more than 50% of waking hours | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status 3=Confined to bed or chair more than 50% of waking | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status 4=Completely disabled | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status 5=Dead | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment Australia | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Canada | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment France | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Italy | 1 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Poland | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Spain | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 5 / 6 | 0 / 7 |
Outcome results
Primary
Progression-Free Survival (PFS)
Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed.
Time frame: Until disease progression, for up to 5 years from randomization
Population: Data could not be reported because the study was terminated early and a sufficient number of subjects and events were not available for analysis.
Secondary
Overall Response Rate (ORR)
Time frame: Until disease progression, for up to 5 years from randomization
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib + Rituximab | Overall Response Rate (ORR) | Complete Response | 3 Participants |
| Duvelisib + Rituximab | Overall Response Rate (ORR) | Partial Response | 2 Participants |
| Duvelisib + Rituximab | Overall Response Rate (ORR) | Stable Disease | 0 Participants |
| Duvelisib + Rituximab | Overall Response Rate (ORR) | Progressive Disease | 0 Participants |
| Placebo + Rituximab | Overall Response Rate (ORR) | Progressive Disease | 2 Participants |
| Placebo + Rituximab | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Placebo + Rituximab | Overall Response Rate (ORR) | Stable Disease | 3 Participants |
| Placebo + Rituximab | Overall Response Rate (ORR) | Partial Response | 1 Participants |