Duvelisib With Obinutuzumab in Patients With CLL/SLL Previously Treated With a BTKi (SYNCHRONY)

Study Overview
=================
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.

Official Title
-----------------
A Phase 1b Study of Duvelisib Administered in Combination With Obinutuzumab in Patients With CLL/SLL Previously Treated With a Bruton's Tyrosine Kinase Inhibitor (BTKi) (SYNCHRONY)

Conditions
-----------------
Lymphocytic Leukemia, Chronic, Lymphoma, Small Lymphocytic

Intervention / Treatment
-----------------
* Drug: IPI-145 (duvelisib)
* Drug: Obinutuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPI-145 in Combination with Obinutuzumab<br> | Drug: IPI-145 (duvelisib)<br>* 25mg and/or 5mg oral capsule<br>* Other names: Duvelisib;Drug: Obinutuzumab<br>* 1000mg/40mL single-use vials<br>* Other names: GAZYVA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLTs) |  | 28 days | 
| Treatment-emergent adverse events (TEAEs) |  | Up to 30 days from last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) |  | Up to 2 years from the first dose of study treatment | 
| Duration of response (DOR) |  | Up to 2 years from the first dose of study treatment | 
| 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 | 
| BTK mutation status |  | Baseline | 
| Pharmacokinetic (PK) parameters of duvelisib and IPI-656 (major metabolite) |  | Week 1, Week 2, Months 2, 4, 7, 11, 15, 19 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase 1b, CLL/SLL, PI3K