Lymphocytic Leukemia, Chronic, Lymphoma, Small Lymphocytic
Conditions
Keywords
Phase 1b, CLL/SLL, PI3K
Brief summary
To evaluate the safety, pharmacokinetics, and pharmacodynamics of Duvelisib (IPI-145) in combination with obinutuzumab in patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma previously treated with a BTKi.
Detailed description
This is a Phase 1b, open-label, dose escalation, safety and tolerability study of Duvelisib (IPI-145) in combination with obinutuzumab in subjects with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma previously treated with a BTKi therapy.
Interventions
25mg and/or 5mg oral capsule
DRUGObinutuzumab
1000mg/40mL single-use vials
Sponsors
SecuraBio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age * Diagnosis of Chronic lymphocytic leukemia or Small lymphocytic lymphoma that meets at least one of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for treatment (Binet Stage ≥ B and/or Rai Stage ≥ I with symptoms) * Measurable disease with a lymph node or tumor mass \>1.5 cm in at least one dimension as assessed by computed tomography (CT) * Previous exposure to BTKi therapy and meets at least one of the below criteria: * Progressive disease while receiving a BTKi therapy, or stable disease as best response after 12 months of receiving a BTKi therapy * Discontinued a BTKi therapy due to BTKi treatment-related intolerance * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status \[KPS\] ≥60%) * Subjects must be able to receive outpatient treatment and laboratory monitoring (where specifically indicated) at the institution that administers study drug for the entire treatment period
Exclusion criteria
* Richter's transformation or prolymphocytic leukemia * Refractory to obinutuzumab (defined as progression or relapse \<12 months of receiving obinutuzumab monotherapy or \<24 months of receiving an obinutuzumab-containing regimen) * Progressive disease while previously receiving a PI3K inhibitor (e.g. GS-1101 \[idelalisib\], duvelisib) or a serious/severe AE related to PI3K inhibitor treatment * History of severe reaction to prior monoclonal antibody therapy (defined as a Grade 4 event and/or requiring permanent discontinuation) * Human immunodeficiency virus (HIV) or Human T Cell Lymphotropic Virus 1 (HTLV-1) infection * Prior, current, or chronic hepatitis B or hepatitis C infection * History of tuberculosis treatment within the preceding 2 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicities (DLTs) | 28 days |
| Treatment-emergent adverse events (TEAEs) | Up to 30 days from last dose of study treatment |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) | Up to 2 years from the first dose of study treatment |
| Overall survival (OS) | Up to 2 years from the first dose of study treatment or until study treatment is completed, whichever is later |
| Overall response rate (ORR) | Up to 2 years from the first dose of study treatment |
| Pharmacokinetic (PK) parameters of duvelisib and IPI-656 (major metabolite) | Week 1, Week 2, Months 2, 4, 7, 11, 15, 19 |
| BTK mutation status | Baseline |
| Duration of response (DOR) | Up to 2 years from the first dose of study treatment |
Countries
Canada, United States
Outcome results
None listed