Follicular Lymphoma (FL), Marginal Zone Lymphoma, Non Hodgkin Lymphoma
Conditions
Brief summary
This is the study of the PI3Kδ inhibitor Zandelisib (ME-401) in subjects with relapsed/refractory follicular lymphoma or marginal zone lymphoma after failure of at least 2 prior lines of systemic therapy
Detailed description
This is a global, multicenter open-label, single-arm, Phase 2 study of the PI3Kδ inhibitor Zandelisib (ME-401) in subjects with relapsed/refractory follicular lymphoma or marginal zone lymphoma after failure of at least 2 prior lines of systemic therapy which must have included an anti-CD20 antibody and chemotherapy with an alkylating agent or a purine analogue. Approximately 180 subjects will be enrolled and treated with Zandelisib (ME-401) on the intermittent schedule.
Interventions
DRUGZandelisib (ME-401)
Zandelisib (ME-401) 60 mg
Sponsors
MEI Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment with Zandelisib (ME-401) (60 mg) given orally once a day on an intermittent schedule
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis as defined in the World Health Organization (WHO) classification scheme 1. Follicular Lymphoma (FL) limited to Grade 1,2 or 3a or 2. Marginal Zone Lymphoma (MZL) including nodal, extranodal and splenic MZL * Subjects that have had progression of disease or had no response to therapy after at least 2 prior systemic therapies for FL or MZL * Age ≥ 18 * At least one bi-dimensionally measurable nodal lesion \> 1.5 cm in its longest diameter by computed tomography (CT) scan as defined by the Lugano Classification * Adequate hematologic, renal and hepatic parameters at screening unless abnormal values are due to FL per Investigator assessment * QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (msec); * Left ventricular ejection fraction (LVEF) ≥ 45%
Exclusion criteria
* Histologically confirmed FL Grade 3b transformation from FL to an aggressive lymphoma * Known lymphomatous involvement of the central nervous system * Uncontrolled clinically significant illness * Ongoing or history of drug-induced pneumonitis * History of clinically significant cardiovascular abnormalities * History of clinically significant GI conditions * Known history of, or active HIV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) of ME-401 in Relapsed or Refractory FL or MZL | 3 years 9 months | ORR is measured as the proportion of subjects achieving the best response rating of CR or PR prior to first PD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | 3 years 9 months | Complete response rate will be measured by the number of subjects that achieve CR |
| Progression-free Survival (PFS) | 3 years 9 months | Progression-free survival will be measurement of time from initiation of treatment (Day 1) until disease progression or death |
| Duration of Response (DOR) | 3 years 9 months | Duration of Response will be measured as the time from documentation from CR or PR to time of disease progression |
| Overall Incidence of Treatment Emergent Adverse Events (TEAEs) | 3 years 9 months | The incidence of TEAEs is measured by the proportion of subjects with at least one TEAE. |
| PK of ME-401 | 3 years 9 months | The PK of ME-401 will be determined by the peak plasma concentration (Cmax) |
| Overall Survival | 2 years | Overall survival will be measured as the time from initiation of treatment (Day 1) until death |
Countries
Australia, Austria, Belgium, France, Germany, Italy, New Zealand, Poland, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This Phase 2 study was open from June 2019 to March 2023 at 124 investigational sites in the United States, United Kingdom, Spain, New Zealand, Austria, South Korea, Belgium, Taiwan, Poland, Italy, Australia, France, Germany. This study was closed prematurely for business reasons . A total of 169 subjects were enrolled. The reasons for subjects not completing the study are listed below. The majority was due to study closure by sponsor.
Participants by arm
| Arm | Count |
|---|---|
| Zandelisib (ME-401) Open Label Subjects with relapsed/refractory FL or MZL will be administered 60 mg of ME-401 orally, once a day on an intermittent schedule (IS).
Zandelisib (ME-401): Zandelisib (ME-401) 60 mg | 169 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 35 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Other -Various | 30 |
| Overall Study | sponsor decision | 76 |
| Overall Study | Withdrawal by Subject | 22 |
Baseline characteristics
| Characteristic | Zandelisib (ME-401) Open Label |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 90 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 24 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 15 Participants |
| Race (NIH/OMB) White | 129 Participants |
| Region of Enrollment Australia | 8 participants |
| Region of Enrollment Austria | 3 participants |
| Region of Enrollment Belgium | 8 participants |
| Region of Enrollment France | 12 participants |
| Region of Enrollment Germany | 4 participants |
| Region of Enrollment Italy | 21 participants |
| Region of Enrollment New Zealand | 5 participants |
| Region of Enrollment Poland | 18 participants |
| Region of Enrollment South Korea | 15 participants |
| Region of Enrollment Spain | 8 participants |
| Region of Enrollment Taiwan | 7 participants |
| Region of Enrollment United Kingdom | 34 participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 63 Participants |
| Sex: Female, Male Male | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 35 / 169 |
| other Total, other adverse events | 162 / 169 |
| serious Total, serious adverse events | 69 / 169 |
Outcome results
Primary
Objective Response Rate (ORR) of ME-401 in Relapsed or Refractory FL or MZL
ORR is measured as the proportion of subjects achieving the best response rating of CR or PR prior to first PD
Time frame: 3 years 9 months
Population: A company decision was made to terminate all Zandelisib studies early due to business reasons including this Phase 2 study. Due to the study being terminated early, no data was collected to analyze ORR
Secondary
Complete Response (CR) Rate
Complete response rate will be measured by the number of subjects that achieve CR
Time frame: 3 years 9 months
Population: A company decision was made to terminate all Zandelisib studies early due to business reasons including this Phase 2 study. Due to the study being terminated early, no data was collected to analyze CR
Secondary
Duration of Response (DOR)
Duration of Response will be measured as the time from documentation from CR or PR to time of disease progression
Time frame: 3 years 9 months
Population: A company decision was made to terminate all Zandelisib studies early due to business reasons including this Phase 2 study. Due to the study being terminated early, no data was collected to analyze DOR
Secondary
Overall Incidence of Treatment Emergent Adverse Events (TEAEs)
The incidence of TEAEs is measured by the proportion of subjects with at least one TEAE.
Time frame: 3 years 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zandelisib (ME-401) Open Label | Overall Incidence of Treatment Emergent Adverse Events (TEAEs) | 162 Participants |
Secondary
Overall Survival
Overall survival will be measured as the time from initiation of treatment (Day 1) until death
Time frame: 2 years
Population: Study was terminated early, therefore data was not available to measure OS at time of termination
Secondary
PK of ME-401
The PK of ME-401 will be determined by the peak plasma concentration (Cmax)
Time frame: 3 years 9 months
Population: A company decision was made to terminate all Zandelisib studies early due to business reasons including this Phase 2 study. Due to the study being terminated early, no data was collected to analyze PK
Secondary
Progression-free Survival (PFS)
Progression-free survival will be measurement of time from initiation of treatment (Day 1) until disease progression or death
Time frame: 3 years 9 months
Population: A company decision was made to terminate all Zandelisib studies early due to business reasons including this Phase 2 study. Due to the study being terminated early, no data was collected to analyze PFS.