Lymphoma
Conditions
Keywords
Follicular lymphoma, non-Hodgkin lymphoma (NHL), phosphatidylinositol 3-kinase (PI3K) δ inhibitor
Brief summary
The purpose of this study is to assess the objective response rate of parsaclisib treatment in participants with relapsed or refractory follicular lymphoma.
Interventions
DRUGParsaclisib
Parsaclisib tablets administered orally with water and without regard to food
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged 18 years or older. * Histologically confirmed, relapsed or refractory, follicular B-cell non-Hodgkin lymphoma (NHL) (follicular lymphoma) Grade 1, 2, and 3a. * Ineligible for hematopoietic stem cell transplant. * Must have been treated with at least 2 prior systemic therapies. * Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures \> 1.5 cm in the longest dimension and ≥ 1.0 cm in the longest perpendicular dimension as assessed by computed tomography or magnetic resonance imaging. * Must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Exclusion criteria
* Known histological transformation from indolent NHL to diffuse large B-cell lymphoma. * History of central nervous system lymphoma (either primary or metastatic). * Prior treatment with idelalisib, other selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors, or a pan-PI3K inhibitor. * Prior treatment with a Bruton's tyrosine kinase inhibitor (eg, ibrutinib). * Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of study treatment administration. * Active graft-versus-host disease. * Participants positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for hepatitis B virus-deoxyribonucleic acid (HBV-DNA). Participants positive for anti-hepatitis C virus (HCV) antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | Up to approximately 148 weeks | ORR=percentage of participants with complete response(CR) or partial response(PR) per revised response criteria for lymphomas,determined by independent review committee(IRC).Criteria for CR:1.Target nodes/nodal masses of lymph nodes,extralymphatic sites regressed to≤1.5cm in longest dimension transverse diameter of lesion(LDi);2.Absence of non-measured lesion;3.Organ enlargement regressed to normal;4.No new lesions;5.Normal bone marrow morphology;if indeterminate,immunohistochemistry negative.Criteria for PR:1.Lymph nodes,extralymphatic sites- ≥50%decrease in sum of product of perpendicular diameters for multiple lesions(SPD)of up to 6 target measurable nodes,extranodal sites;if lesion is too small to measure on computed tomography(CT),assign5mm×5mm as default;if no longer visible,0×0mm.Node\>5mm×5mm but smaller than normal,use actual measurement.2.Absent/regressed non-measured lesions,no increase.3.Organ enlargement-Spleen regressed by\>50%in length beyond normal.4.No new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to 1193 days | DOR=time from first documented evidence of CR or PR until disease progression or death from any cause among participants who achieve an objective response as determined by IRC. Criteria for CR: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. The criteria for PR included: 1.Lymph nodes and extralymphatic sites- a. ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; b. when a lesion is too small to measure on CT, assign 5 mm×5 mm as the default; c.when no longer visible, 0×0 mm. For a node \>5 mm×5 mm but smaller than normal, use actual measurement. 2.Non-measured lesions- Absent/regressed, but no increase. 3. Organ enlargement-Spleen must have regressed by \>50% in length beyond normal. 4.No new lesions. |
| Progression-free Survival (PFS) With Parsaclisib | Up to 1193 days | PFS was defined as the time from the date of the first dose of study treatment until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause. |
| Complete Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | Up to 1193 days | CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphomas as determined by an IRC. The criteria for CR included: 1. Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3. Organ enlargement regressed to normal; 4. No new lesions; 5. Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. |
| Best Percent Change From Baseline in Target Lesion Size | Up to 1193 days | Target lesion size is measured by the sum of the product of diameters of all target lesion sizes and is determined by the IRC. The best percent change from Baseline is defined as the largest decrease, or smallest increase (if no decrease available), from Baseline in target lesion sizes on/before new (next-line) anti-lymphoma therapy during the study. Baseline is the last non-missing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement. |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | up to approximately 1992 days | An adverse event (AE) is defined as any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. TEAE is any AE either reported for first time or worsening of a pre-existing event after first dose of study drug and within 30 days of last administration of study drug regardless of starting new anti-lymphoma therapy. SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention. |
| Overall Survival (OS) With Parsaclisib | Up to 1193 days | OS was defined as the time from the date of the first dose of study treatment until death from any cause. |
Countries
Australia, Canada, Czechia, Denmark, Germany, Hungary, Israel, Italy, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 44 investigative sites in the United States, Italy, Spain, Great Britain, Czech Republic, Hungary, Canada, Denmark, Germany, Israel, Poland, and Sweden
Pre-assignment details
A total of 126 participants with relapsed or refractory follicular lymphoma were enrolled in the study and assigned to one of two treatment groups: Treatment A or Treatment B to receive parsaclisib.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW Participants received parsaclisib 20 milligrams (mg) once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to approximately 52 weeks. | 23 |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD Participants received parsaclisib 20 mg QD for 8 weeks followed by 2.5 mg QD for up to approximately 52 weeks. | 103 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 27 |
| Overall Study | Did Not Return to Site for Care | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Site Closed | 0 | 1 |
| Overall Study | Transitioned to Rollover Study | 0 | 11 |
| Overall Study | Withdrawal by Subject | 1 | 9 |
Baseline characteristics
| Characteristic | Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Total |
|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 11.56 | 67.0 years STANDARD_DEVIATION 10.68 | 66.5 years STANDARD_DEVIATION 10.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 90 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 7 Participants | 10 Participants |
| Race Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race Customized Black/ African- American | 1 Participants | 6 Participants | 7 Participants |
| Race Customized Unavailable or Unknown | 1 Participants | 4 Participants | 5 Participants |
| Race Customized White/ Caucasian | 21 Participants | 92 Participants | 113 Participants |
| Sex: Female, Male Female | 11 Participants | 45 Participants | 56 Participants |
| Sex: Female, Male Male | 12 Participants | 58 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 23 | 27 / 103 |
| other Total, other adverse events | 22 / 23 | 94 / 103 |
| serious Total, serious adverse events | 12 / 23 | 55 / 103 |
Outcome results
Primary
Objective Response Rate With Parsaclisib Based on Lugano Classification Response Criteria
ORR=percentage of participants with complete response(CR) or partial response(PR) per revised response criteria for lymphomas,determined by independent review committee(IRC).Criteria for CR:1.Target nodes/nodal masses of lymph nodes,extralymphatic sites regressed to≤1.5cm in longest dimension transverse diameter of lesion(LDi);2.Absence of non-measured lesion;3.Organ enlargement regressed to normal;4.No new lesions;5.Normal bone marrow morphology;if indeterminate,immunohistochemistry negative.Criteria for PR:1.Lymph nodes,extralymphatic sites- ≥50%decrease in sum of product of perpendicular diameters for multiple lesions(SPD)of up to 6 target measurable nodes,extranodal sites;if lesion is too small to measure on computed tomography(CT),assign5mm×5mm as default;if no longer visible,0×0mm.Node\>5mm×5mm but smaller than normal,use actual measurement.2.Absent/regressed non-measured lesions,no increase.3.Organ enlargement-Spleen regressed by\>50%in length beyond normal.4.No new lesions.
Time frame: Up to approximately 148 weeks
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Objective Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | 65.2 percentage of participants |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Objective Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | 77.7 percentage of participants |
Secondary
Best Percent Change From Baseline in Target Lesion Size
Target lesion size is measured by the sum of the product of diameters of all target lesion sizes and is determined by the IRC. The best percent change from Baseline is defined as the largest decrease, or smallest increase (if no decrease available), from Baseline in target lesion sizes on/before new (next-line) anti-lymphoma therapy during the study. Baseline is the last non-missing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement.
Time frame: Up to 1193 days
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib. The overall number of participants analyzed is the number of participants with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Best Percent Change From Baseline in Target Lesion Size | -72.90 percent change in lesion size | Standard Deviation 21.782 |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Best Percent Change From Baseline in Target Lesion Size | -72.77 percent change in lesion size | Standard Deviation 31.972 |
Secondary
Complete Response Rate With Parsaclisib Based on Lugano Classification Response Criteria
CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphomas as determined by an IRC. The criteria for CR included: 1. Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3. Organ enlargement regressed to normal; 4. No new lesions; 5. Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative.
Time frame: Up to 1193 days
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Complete Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | 17.4 percentage of participants |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Complete Response Rate With Parsaclisib Based on Lugano Classification Response Criteria | 22.3 percentage of participants |
Secondary
Duration of Response (DOR)
DOR=time from first documented evidence of CR or PR until disease progression or death from any cause among participants who achieve an objective response as determined by IRC. Criteria for CR: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. The criteria for PR included: 1.Lymph nodes and extralymphatic sites- a. ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; b. when a lesion is too small to measure on CT, assign 5 mm×5 mm as the default; c.when no longer visible, 0×0 mm. For a node \>5 mm×5 mm but smaller than normal, use actual measurement. 2.Non-measured lesions- Absent/regressed, but no increase. 3. Organ enlargement-Spleen must have regressed by \>50% in length beyond normal. 4.No new lesions.
Time frame: Up to 1193 days
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib. Only participants with objective response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Duration of Response (DOR) | 14.06 months |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Duration of Response (DOR) | 14.72 months |
Secondary
Overall Survival (OS) With Parsaclisib
OS was defined as the time from the date of the first dose of study treatment until death from any cause.
Time frame: Up to 1193 days
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Overall Survival (OS) With Parsaclisib | NA months |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Overall Survival (OS) With Parsaclisib | NA months |
Secondary
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is defined as any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. TEAE is any AE either reported for first time or worsening of a pre-existing event after first dose of study drug and within 30 days of last administration of study drug regardless of starting new anti-lymphoma therapy. SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.
Time frame: up to approximately 1992 days
Population: Safety Population: all participants enrolled in the study who received at least 1 dose of parsaclisib
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 100.0 percentage of participants |
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 52.2 percentage of participants |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 99.0 percentage of participants |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 53.4 percentage of participants |
Secondary
Progression-free Survival (PFS) With Parsaclisib
PFS was defined as the time from the date of the first dose of study treatment until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause.
Time frame: Up to 1193 days
Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW | Progression-free Survival (PFS) With Parsaclisib | 19.32 months |
| Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD | Progression-free Survival (PFS) With Parsaclisib | 14.03 months |