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

Phase 1

Terminated

• Conditions: Lymphoma, Small Lymphocytic; Lymphocytic Leukemia, Chronic
• Interventions: Drug: IPI-145 (duvelisib); Drug: Obinutuzumab

• Registration Number: NCT02292225
• Lead Sponsor: SecuraBio

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.

Study Timeline

• Study First Submitted: 2014-11-10
• Study First Submitted QC: 2014-11-12
• Study First Posted: 2014-11-17
• Study Start: 2015-02
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-24
• Last Update Posted: 2023-02-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IPI-145 in Combination with Obinutuzumab	IPI-145 (duvelisib)	-
IPI-145 in Combination with Obinutuzumab	Obinutuzumab	-

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicities (DLTs)	28 days
Treatment-emergent adverse events (TEAEs)	Up to 30 days from last dose of study treatment

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) parameters of duvelisib and IPI-656 (major metabolite)	Week 1, Week 2, Months 2, 4, 7, 11, 15, 19
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
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 response rate (ORR)	Up to 2 years from the first dose of study treatment