Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma
Conditions
Keywords
Diffuse large B-cell lymphoma, Mantle cell lymphoma, Follicular lymphoma, PI3K inhibitor, Non-Hodgkin lymphoma, NHL
Brief summary
This is a phase II study evaluating the safety, tolerability and efficacy of BKM120 in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) or follicular lymphoma (FL).
Interventions
DRUGBuparlisib
100 mg hard gelatin capsules administered orally, once daily in cycles of 28 days
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient had a histologically confirmed diagnosis of mantle cell lymphoma, follicular lymphoma, or diffuse large B cell lymphoma. 2. Patient had relapsed or refractory disease and received at least one prior therapy. 3. Patient with diffuse large B cell lymphoma had received or was ineligible for autologous or allogeneic stem cell transplant. 4. Patient had at least one measurable nodal lesion (≥2 cm) according to Cheson criteria (Cheson 2007). In case where the patient had no measurable nodal lesions ≥ 2 cm in the long axis at baseline, then the patient must have had at least one measurable extra-nodal lesion. 5. Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 6. Patient had adequate bone marrow and organ function.
Exclusion criteria
1. Patient had received previous treatment with PI3K inhibitors 2. Patient had evidence of graft versus host disease (GVHD). 3. Patient had active or history of central nervous system (CNS) disease. 4. Patient had a concurrent malignancy or had a malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer). 5. Patient had a score ≥ 12 on the PHQ-9 questionnaire. 6. Patient had a GAD-7 mood scale score ≥ 15. 7. Pregnant or nursing women 8. Patient who did not use highly effective contraception methods to avoid becoming pregnant or conceiving offspring.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | Baseline up to 6 months | Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression- Free Survival (PFS) Based on Investigator Assessment (FAS) | Baseline up to approximately 44 months | Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort. |
| Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS) | Baseline up to approximately 18 months | Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause |
| Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | Baseline up to approximately 44 months | Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit |
| Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | Baseline up to approximately 18 months | Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals |
| Overall Survival - Median (FAS) | Baseline up approximately 44 months | Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals |
Countries
Belgium, France, Germany, Italy, South Korea, Spain, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
Primary reason for not completing is presented
Participants by arm
| Arm | Count |
|---|---|
| DLBCL Cohort Diffuse large B-cell lymphoma cohort | 26 |
| MCL Cohort Mantle cell lymphoma cohort | 22 |
| FL Cohort Follicular lymphoma cohort | 24 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 11 | 5 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Disease progression | 11 | 8 | 7 |
| Overall Study | Physician Decision | 1 | 1 | 4 |
| Overall Study | Protocol Violation | 5 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 5 |
| Overall Study | Withdrawal by subject/guardian | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | MCL Cohort | FL Cohort | DLBCL Cohort | Total |
|---|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 8.56 | 61.4 years STANDARD_DEVIATION 13.11 | 60.0 years STANDARD_DEVIATION 14.57 | 62.9 years STANDARD_DEVIATION 12.8 |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 21 Participants | 19 Participants | 57 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Male | 18 Participants | 13 Participants | 18 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 26 | 1 / 22 | 0 / 24 |
| other Total, other adverse events | 25 / 26 | 22 / 22 | 23 / 24 |
| serious Total, serious adverse events | 12 / 26 | 12 / 22 | 7 / 24 |
Outcome results
Primary
Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS)
Overall Response rate is the percentage of patients in a cohort who experienced either complete response (CR) or partial response (PR) during their follow-up after treatment start divided by the total percentage of patients included in the corresponding cohort according to Cheson criteria The analysis for each cohort was based on an exact binomial test comparing the ORR to the reference level of 10% (null hypothesis) in the FAS. The test for each cohort used a significance level of 5%. The ORR was presented together with an exact 95% Clopper- Pearson confidence interval. Disease Control Rate (DCR progressive. Disease Control Rate (DCR) was the percentage of patients with CR, PR or SD (stable disease). Patients for whom the best response after treatment start was missing, unknown (UNK) or progressive disease (PD) were considered non-responders and were counted in the denominator for the estimation of the ORR
Time frame: Baseline up to 6 months
Population: different numbers represents satisfying particular criteria
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DLBCL Cohort | Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | ORR | 11.5 percentage of participants |
| DLBCL Cohort | Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | DCR | 30.8 percentage of participants |
| MCL Cohort | Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | DCR | 81.8 percentage of participants |
| MCL Cohort | Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | ORR | 22.7 percentage of participants |
| FL Cohort | Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | DCR | 87.5 percentage of participants |
| FL Cohort | Overall Response Rate (ORR) and Disease Control Rate (DCR) Per Investigator at 6 Months (FAS) | ORR | 25.0 percentage of participants |
Secondary
Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS)
Duration of response is the time from the date of first occurrence of complete response (CR) or partial response (PR) to the date of the first documented progressive disease (PD) or death due to any cause
Time frame: Baseline up to approximately 18 months
Population: Number analyzed represents participants satisfying criteria for duration of response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DLBCL Cohort | Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS) | 2.2 months |
| MCL Cohort | Duration of Response for Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL) Cohorts (FAS) | 11.0 months |
Secondary
Overall Survival - Median (FAS)
Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
Time frame: Baseline up approximately 44 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DLBCL Cohort | Overall Survival - Median (FAS) | 5.2 months |
| MCL Cohort | Overall Survival - Median (FAS) | NA months |
| FL Cohort | Overall Survival - Median (FAS) | NA months |
Secondary
Overall Survival (OS) - Percentage of Participants With OS Events (FAS)
Overall survival (OS) is the time from treatment start to the date of death due to any cause. Participants not known to have died were censored at the date of their last visit
Time frame: Baseline up to approximately 44 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DLBCL Cohort | Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | OS events | 50.0 percentage of participants |
| DLBCL Cohort | Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | Number censored | 50.0 percentage of participants |
| MCL Cohort | Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | OS events | 22.7 percentage of participants |
| MCL Cohort | Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | Number censored | 77.3 percentage of participants |
| FL Cohort | Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | OS events | 8.3 percentage of participants |
| FL Cohort | Overall Survival (OS) - Percentage of Participants With OS Events (FAS) | Number censored | 91.7 percentage of participants |
Secondary
Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS)
Overall survival (OS) is the time from treatment start to the date of death due to any cause. Estimates done by cohort using Kaplan-Meier method with 95% confidence intervals
Time frame: Baseline up to approximately 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DLBCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 12 month | 43.8 percentage of participants |
| DLBCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 18 month | 43.8 percentage of participants |
| DLBCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 2 month | 83.6 percentage of participants |
| DLBCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 4 month | 66.9 percentage of participants |
| DLBCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 6 month | 43.8 percentage of participants |
| MCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 12 month | 77.8 percentage of participants |
| MCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 6 month | 90.2 percentage of participants |
| MCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 4 month | 90.2 percentage of participants |
| MCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 18 month | 70.1 percentage of participants |
| MCL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 2 month | 100.0 percentage of participants |
| FL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 18 month | 95.2 percentage of participants |
| FL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 2 month | 100.0 percentage of participants |
| FL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 4 month | 100.0 percentage of participants |
| FL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 6 month | 95.2 percentage of participants |
| FL Cohort | Percentage of Participants - Overall Survival- Kaplan Meier Estimates (FAS) | 12 month | 95.2 percentage of participants |
Secondary
Progression- Free Survival (PFS) Based on Investigator Assessment (FAS)
Progression-free survival (PFS) is the time from the date of treatment start to the date of the first documented progressive disease (PD) or death due to any cause using Kaplan-Meier method by cohort.
Time frame: Baseline up to approximately 44 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DLBCL Cohort | Progression- Free Survival (PFS) Based on Investigator Assessment (FAS) | 1.8 months |
| MCL Cohort | Progression- Free Survival (PFS) Based on Investigator Assessment (FAS) | 11.3 months |
| FL Cohort | Progression- Free Survival (PFS) Based on Investigator Assessment (FAS) | 9.1 months |