Follicular Lymphoma (FL), Marginal Zone Lymphoma, Non Hodgkin Lymphoma
Conditions
Brief summary
This is a Phase 3 study of the PI3Kδ inhibitor Zandelisib (ME-401) in combination with rituximab, in comparison to standard immunochemotherapy (Rituximab-Bendamustine or Rituximab-CHOP) in subjects with relapsed or refractory FL and MZL.
Detailed description
This is an open label, randomized, two-arm Phase 3 study in subjects with relapsed or refractory FL and MZL to evaluate efficacy and safety of zandelisib in combination with rituximab in comparison to standard immunochemotherapy (Rituximab-Bendamustine or Rituximab-CHOP). Subjects must have relapsed after at least one previous line of systemic immunochemotherapy. Previous treatments must have included an anti-CD20 monoclonal antibody (mAb) with chemotherapy such as Bendamustine (B), CHOP, CVP, FND, or similar regimens, or an anti-CD20 mAb with Lenalidomide (L). Approximately 534 randomized subjects will be enrolled in this study.
Interventions
DRUGZandelisib
Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3
DRUGRituximab
Rituximab IV 375 mg/m2 for 6 cycles
DRUGBendamustine
Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles
DRUGCHOP
Cyclophosphamide, Vindcristine IV, and Prednisone daily orally
Sponsors
Kyowa Kirin, Inc.
MEI Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arm 1: Rituximab plus Zandelisib Arm 2: Rituximab plus chemotherapy (CHOP or Bendamustine)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects ≥18 years of age, ≥19 years in Korea, or ≥20 years for subjects in Japan and Taiwan * Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to: 1. FL Gr 1, Gr 2, or Gr 3a 2. MZL (splenic, nodal, or extra-nodal) * Subjects with relapsed or refractory disease who received ≥1 prior lines of therapy * Subjects must have at least one bi-dimensionally measurable lesion \>1.5 cm * Adequate hematologic parameters at screening unless abnormal values are due to disease * Adequate renal and hepatic function * Adequate cardiac function based on ECG and LVEF assessments
Exclusion criteria
* Histologically confirmed diagnosis of FL Gr 3b or transformed disease * Prior therapy with PI3K inhibitors * Ongoing or history of drug-induced pneumonitis * Known lymphomatous involvement of the central nervous system * Tested positive for or active viral infection with hepatitis B or C virus * Tested positive or active infection with human immunodeficiency virus * Tested positive, or active infection with human T-cell leukemia virus type 1 * Any uncontrolled clinically significant illness * History of clinically significant cardiovascular abnormalities such as congestive heart failure * History of clinically significant gastrointestinal (GI) conditions * Females who are pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 1 year 7 months | PFS is defined as the time from randomization date until the date of disease progression, or death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Lab Abnormalities (Zandelisib When Combined With Rituximab) | 1 year 7 months | Measured by the number of laboratory abnormalities |
| Overall Response Rate (ORR) | 1 year 7 months | ORR is defined as the proportion of subjects who have a best overall response of CR or PR according to the Lugano Classification over the entire duration of the study, including the efficacy follow-up period. |
| Complete Response Rate (CRR) | 1 year 7 months | CRR is defined as the proportion of subjects who have a best overall response of CR during the study (i.e., up to time of analysis of PFS). |
| Overall Survival | 1 year 7 months | OS is defined as the time (in days) from randomization until death from any cause. For subjects alive at the time of analysis, they will be censored at the last documented alive date. |
| Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab) | 1 year 7 months | Measured by the number of Treatment Emergent AEs |
| Number of SAEs (Zandelisib When Combined With Rituximab) | 1 year 7 months | Measured by the number of SAEs |
Countries
Australia, Belgium, Canada, France, Georgia, Greece, Hungary, Italy, Japan, Netherlands, New Zealand, Poland, Serbia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study was open from August 2021 through March 2023 at 144 investigational sites in the US, Argentina, Australia, Belgium, Canada, Czech Republic France Georgia, Germany, Greece, Hungary, Ireland, Italy, Japan, Korea, Netherlands, Poland, Serbia, Spain, Taiwan, Turkey, and UK Originally, it was anticipated that approximately 534 subjects would be randomized into the study however the study was terminated for business reasons with 82 subjects enrolled and dosed.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Plus Zandelisib Rituximab plus Zandelisib for 6 cycles followed by Zandelisib for 20 cycles
Zandelisib: Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3
Rituximab: Rituximab IV 375 mg/m2 for 6 cycles | 41 |
| Rituximab Plus Chemotherapy Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles
Rituximab: Rituximab IV 375 mg/m2 for 6 cycles
Bendamustine: Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles
CHOP: Cyclophosphamide, Vindcristine IV, and Prednisone daily orally | 41 |
| Total | 82 |
Baseline characteristics
| Characteristic | Rituximab Plus Zandelisib | Total | Rituximab Plus Chemotherapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 42 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 40 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 34 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) White | 21 Participants | 40 Participants | 19 Participants |
| Region of Enrollment Belgium | 3 participants | 4 participants | 1 participants |
| Region of Enrollment France | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Georgia | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Hungary | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Italy | 5 participants | 8 participants | 3 participants |
| Region of Enrollment Japan | 10 participants | 17 participants | 7 participants |
| Region of Enrollment Netherlands | 1 participants | 1 participants | 0 participants |
| Region of Enrollment New Zealand | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Poland | 1 participants | 5 participants | 4 participants |
| Region of Enrollment Serbia | 5 participants | 8 participants | 3 participants |
| Region of Enrollment South Korea | 5 participants | 15 participants | 10 participants |
| Region of Enrollment Spain | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Taiwan | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Turkey | 1 participants | 4 participants | 3 participants |
| Region of Enrollment United Kingdom | 4 participants | 6 participants | 2 participants |
| Region of Enrollment United States | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 24 Participants | 49 Participants | 25 Participants |
| Sex: Female, Male Male | 17 Participants | 33 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 41 | 1 / 41 |
| other Total, other adverse events | 38 / 41 | 37 / 41 |
| serious Total, serious adverse events | 12 / 41 | 8 / 41 |
Outcome results
Primary
Progression Free Survival
PFS is defined as the time from randomization date until the date of disease progression, or death from any cause
Time frame: 1 year 7 months
Population: A decision was made to terminate this Phase 3 study early due to business reasons. For the 82 subjects enrolled no scans had been collected at the time of termination, therefore no data were analyzed.
Secondary
Complete Response Rate (CRR)
CRR is defined as the proportion of subjects who have a best overall response of CR during the study (i.e., up to time of analysis of PFS).
Time frame: 1 year 7 months
Population: A decision was made to terminate this Phase 3 study early due to business reasons. For the 84 subjects enrolled no scans had been collected at the time of termination, therefore no data were analyzed.
Secondary
Number of Lab Abnormalities (Zandelisib When Combined With Rituximab)
Measured by the number of laboratory abnormalities
Time frame: 1 year 7 months
Population: A decision was made to terminate this Phase 3 study early due to business reasons. For the 82 subjects enrolled no lab abnormalities had been collected or analyzed
Secondary
Number of SAEs (Zandelisib When Combined With Rituximab)
Measured by the number of SAEs
Time frame: 1 year 7 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab Plus Zandelisib | Number of SAEs (Zandelisib When Combined With Rituximab) | 12 Participants |
| Rituximab Plus Chemotherapy | Number of SAEs (Zandelisib When Combined With Rituximab) | 8 Participants |
Secondary
Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab)
Measured by the number of Treatment Emergent AEs
Time frame: 1 year 7 months
Population: Of the 41 subjects enrolled to the R+Zandelisib group 38 had a Treatment Emergent AE Of the 41 subjects enrolled to the R-Chemo group 37 had a Treatment Emergent AE
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab Plus Zandelisib | Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab) | 38 Participants |
| Rituximab Plus Chemotherapy | Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab) | 37 Participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the proportion of subjects who have a best overall response of CR or PR according to the Lugano Classification over the entire duration of the study, including the efficacy follow-up period.
Time frame: 1 year 7 months
Population: A decision was made to terminate this Phase 3 study early due to business reasons. For the 82 subjects enrolled no scans had been collected at the time of termination, therefore no data were analyzed.
Secondary
Overall Survival
OS is defined as the time (in days) from randomization until death from any cause. For subjects alive at the time of analysis, they will be censored at the last documented alive date.
Time frame: 1 year 7 months
Population: A decision was made to terminate this Phase 3 study early due to business reasons, therefore no data were collected or analyzed.