Clinical trial NCT02292225: Duvelisib With Obinutuzumab in Patients With CLL/SLL Previously Treated With a BTKi (SYNCHRONY)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphocytic Leukemia, Chronic
Lymphoma, Small Lymphocytic
Keywords: Phase 1b, CLL/SLL, PI3K
Lead sponsor: SecuraBio
Sponsor class: INDUSTRY
First posted: 2014-11-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Dose-limiting toxicities (DLTs)
timeFrame: 28 days
measure: Treatment-emergent adverse events (TEAEs)
timeFrame: Up to 30 days from last dose of study treatment
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 2 years from the first dose of study treatment
measure: Duration of response (DOR)
timeFrame: Up to 2 years from the first dose of study treatment
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years from the first dose of study treatment
measure: Overall survival (OS)
timeFrame: Up to 2 years from the first dose of study treatment or until study treatment is completed, whichever is later
measure: BTK mutation status
timeFrame: Baseline
measure: Pharmacokinetic (PK) parameters of duvelisib and IPI-656 (major metabolite)
timeFrame: Week 1, Week 2, Months 2, 4, 7, 11, 15, 19
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Boston
country: United States
state: Massachusetts
city: Hackensack
country: United States
state: New Jersey
city: New Hyde Park
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Montreal
country: Canada
state: Quebec
Study officials:
References: