CD20+ Follicular Lymphoma
Conditions
Keywords
Follicular Lymphoma, Previously Untreated
Brief summary
A Two-arm, Phase 1b/2 Study of duvelisib Administered in Combination with Rituximab or Obinutuzumab in Subjects with Previously Untreated CD20+ Follicular Lymphoma.
Detailed description
This is a two-arm, open-label, Phase 1b/2 trial designed to evaluate the safety and efficacy of duvelisib in combination with rituximab and duvelisib in combination with obinutuzumab in subjects with previously untreated CD20+ FL. The study will be conducted in two parts, a Safety Lead-in (Part 1) followed by a randomized, 2-Stage Design in Part 2. Each treatment arm will be assessed independently for dose limiting toxicity (DLT) within Part 1.
Interventions
DRUGDuvelisib
PI3K Inhibitor
DRUGRituximab
monoclonal antibody
DRUGObinutuzumab
monoclonal antibody
Sponsors
SecuraBio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of CD20+, follicular lymphoma that has not been treated * CD20-immunophenotyping of tumor to document B-cell follicular lymphoma * Stage II disease with bulky disease (≥ 7cm lesion), Stage III, or Stage IV disease * Disease that requires treatment based on the Investigator's opinion (e.g., meets GELF criteria) * At least one measurable lesion that is \> 1.5 cm in at least one dimension * Eastern Cooperative Oncology Group (ECOG) performance status \<=2 (corresponds to Karnofsky Performance Status \[KPS\] \>=60%)
Exclusion criteria
* Received systemic treatment for lymphoma such as chemotherapy, immunotherapy, radiotherapy, investigational agents, or radioimmunotherapy. * Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B follicular lymphoma * Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs * Prior allogeneic hematopoietic stem cell transplant * Prior, current or chronic hepatitis B or hepatitis C infection * Human immunodeficiency virus (HIV) infection or Human T Cell Lymphotropic Virus 1 (HTLV-1) infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects With Dose Limiting Toxicities (DLTs) - Part 1 | 28 days from first dose of study treatment |
| Complete Response Rate (CRR)- Part 2 | Up to 2 years from the first dose of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to 2 years from the first dose of study treatment | The median DOR was non-estimable. |
| Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | Up to 30 days after the last dose of study treatment | Composite measure of safety, as indicated by Treatment-emergent adverse events (TEAEs) and changes in safety laboratory values. TEAEs assessed as \>=Grade 3. |
| Pharmacokinetic (PK): Plasma Concentrations of Duvelisib and IPI-656 (Metabolite) | Every 4 weeks for 16 weeks | Plasma concentrations of Duvelisib and IPI-656 (metabolite) |
| Overall Survival (OS) | Up to 2 years from the first dose of study treatment | — |
| Overall Response Rate (ORR) | Up to 2 years from the first dose of study treatment | — |
Countries
Belgium, France, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Duvelisib and Obinutuzumab Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Duvelisib will be administered orally, twice daily, in 28-day cycles.
Obinutuzumab 1000 mg will be administered intravenously (IV) beginning at Cycle 1 (28 day cycles); days 1, 8, 15 and 22. Thereafter, infusions will occur on Day 1 of the even cycles treatment; Cycles 4-26.
IPI-145 (duvelisib): PI3K Inhibitor
Obinutuzumab | 27 |
| Duvelisib and Rituximab Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Duvelisib will be administered orally, twice daily, in 28-day cycles.
Rituximab 375 mg/m2 will be administered intravenously (IV) beginning on Cycle 1 (28 day cycles); days 1, 8, 15 and 22. Thereafter, infusions will occur on Day 1 of the even cycles treatment; Cycles 4-26.
IPI-145 (duvelisib): PI3K Inhibitor
Rituximab | 28 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other Reasons | 6 | 4 |
| Overall Study | Termination of study by sponsor | 20 | 20 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Duvelisib and Obinutuzumab | Duvelisib and Rituximab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 8 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 20 Participants | 36 Participants |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 12.32 | 58.2 years STANDARD_DEVIATION 10.65 | 58.3 years STANDARD_DEVIATION 11.39 |
| Region of Enrollment Belgium | 6 participants | 3 participants | 9 participants |
| Region of Enrollment France | 3 participants | 4 participants | 7 participants |
| Region of Enrollment Italy | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Spain | 4 participants | 9 participants | 13 participants |
| Region of Enrollment United Kingdom | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United States | 10 participants | 9 participants | 19 participants |
| Sex: Female, Male Female | 16 Participants | 10 Participants | 26 Participants |
| Sex: Female, Male Male | 11 Participants | 18 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 1 / 28 |
| other Total, other adverse events | 26 / 27 | 27 / 28 |
| serious Total, serious adverse events | 16 / 27 | 10 / 28 |
Outcome results
Primary
Complete Response Rate (CRR)- Part 2
Time frame: Up to 2 years from the first dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib and Obinutuzumab | Complete Response Rate (CRR)- Part 2 | 11 Participants |
| Duvelisib and Rituximab | Complete Response Rate (CRR)- Part 2 | 10 Participants |
Primary
Number of Subjects With Dose Limiting Toxicities (DLTs) - Part 1
Time frame: 28 days from first dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Duvelisib and Obinutuzumab | Number of Subjects With Dose Limiting Toxicities (DLTs) - Part 1 | 1 Participants |
| Duvelisib and Rituximab | Number of Subjects With Dose Limiting Toxicities (DLTs) - Part 1 | 0 Participants |
Secondary
Duration of Response (DOR)
The median DOR was non-estimable.
Time frame: Up to 2 years from the first dose of study treatment
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: Up to 2 years from the first dose of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duvelisib and Obinutuzumab | Overall Response Rate (ORR) | Complete Response | 11 participants |
| Duvelisib and Obinutuzumab | Overall Response Rate (ORR) | Partial Response | 13 participants |
| Duvelisib and Obinutuzumab | Overall Response Rate (ORR) | Stable Disease | 1 participants |
| Duvelisib and Rituximab | Overall Response Rate (ORR) | Complete Response | 10 participants |
| Duvelisib and Rituximab | Overall Response Rate (ORR) | Partial Response | 16 participants |
| Duvelisib and Rituximab | Overall Response Rate (ORR) | Stable Disease | 0 participants |
Secondary
Overall Survival (OS)
Time frame: Up to 2 years from the first dose of study treatment
Population: The study had been terminated and Overall Survival was not performed.
Secondary
Pharmacokinetic (PK): Plasma Concentrations of Duvelisib and IPI-656 (Metabolite)
Plasma concentrations of Duvelisib and IPI-656 (metabolite)
Time frame: Every 4 weeks for 16 weeks
Population: The study had been terminated and PK analysis was not performed.
Secondary
Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values
Composite measure of safety, as indicated by Treatment-emergent adverse events (TEAEs) and changes in safety laboratory values. TEAEs assessed as \>=Grade 3.
Time frame: Up to 30 days after the last dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Duvelisib and Obinutuzumab | Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | TEAEs assessed as ≥ Grade 3 | 24 Participants |
| Duvelisib and Obinutuzumab | Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | TEAEs ≥ Grade 3 assessed as related to duvelisib | 23 Participants |
| Duvelisib and Obinutuzumab | Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | TEAEs ≥ Grade 3 assessed as related to anti-CD20 | 11 Participants |
| Duvelisib and Rituximab | Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | TEAEs assessed as ≥ Grade 3 | 19 Participants |
| Duvelisib and Rituximab | Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | TEAEs ≥ Grade 3 assessed as related to duvelisib | 17 Participants |
| Duvelisib and Rituximab | Safety: Composite Measure of Safety, as Indicated by Treatment-emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values | TEAEs ≥ Grade 3 assessed as related to anti-CD20 | 2 Participants |