Clinical trial NCT01799889: Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies
Official title: A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Subjects With Relapsed or Refractory Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Diffuse Large B-cell Lymphoma
Non-FL Indolent Non-Hodgkin's Lymphoma
Follicular Lymphoma
Keywords: SYK inhibitor
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-02-27
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate efficacy of entospletinib in participants with relapsed or refractory hematologic malignancies. Participants with the following relapsed or refractory hematologic malignancies will be enrolled into the study: relapsed or refractory chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or non-FL indolent non-Hodgkin lymphomas (iNHL; including lymphoplasmacytoid lymphoma/ Waldenström macroglobulinemia \[LPL/WM\], small lymphocytic lymphoma \[SLL\], or marginal zone lymphoma \[MZL\]).


Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of B-cell iNHL, DLBCL, MCL, or CLL as documented by medical records and with histology based on criteria established by the World Health Organization
* For institutions that have Phase 3 or Phase 4 protocols studying idelalisib (Zydelig®) ; individuals with malignancies being studied in these protocols must have failed screening in the respective idelalisib protocol
* Prior treatment for lymphoid malignancy requiring treatment for progressive disease
* Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
* All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study drug
* Karnofsky performance status of ≥ 60
* Life expectancy of at least 3 months

Key Exclusion Criteria:

* Known histological transformation from iNHL or CLL to an aggressive form of non-Hodgkin lymphoma (ie, Richter transformation) except if the CLL participant is enrolling in the BCR previously treated cohort
* Known active central nervous system or leptomeningeal lymphoma
* Presence of known intermediate- or high-grade myelodysplastic syndrome
* Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study drug
* Ongoing liver injury
* Ongoing or recent hepatic encephalopathy
* Ongoing drug-induced pneumonitis
* Ongoing inflammatory bowel disease
* Ongoing alcohol or drug addiction
* Pregnancy or breastfeeding
* History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
* Ongoing immunosuppressive therapy
* Concurrent participation in an investigational drug trial with therapeutic intent

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Progression-Free Survival (PFS) Rate of Participants With CLL After BCR Targeted Therapy, MCL, and DLBCL at Week 16
timeFrame: Week 16
measure: PFS Rate of Participants With CLL (Including CLL, Prior BCR Inhibitor Naive Participants), FL, and Non-FL iNHL at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to the last dose date plus 30 days (maximum: 78.4 months)
measure: Percentage of Participants With Hematology Postbaseline Toxicity Grade 3 or Higher
timeFrame: First dose date up to the last dose date plus 30 days (maximum: 78.4 months)
measure: Percentage of Participants With Serum Chemistry Toxicity Postbaseline Grade 3 or Higher
timeFrame: First dose date up to the last dose date plus 30 days (maximum: 78.4 months)
measure: Objective Response Rate (ORR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
timeFrame: From first dose date until first occurrence of CR or PR (or VGPR or MR for participants with LPL/WM) (up to approximately 7 years)
measure: Duration of Response (DOR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
timeFrame: From the date of first documentation of CR or PR (or VGPR or MR for participants with LPL/WM) to disease progression or death from any cause (up to approximately 7 years)
measure: Time to Response (TTR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
timeFrame: From the first dose of study drug to the first documentation of CR or PR (or VGPR or MR for participants with LPL/WM) (up to approximately 7 years)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Denver
country: United States
facility: Kaiser Permanente of Colorado
state: Colorado
city: Southington
country: United States
facility: Cancer Center of Central Connecticut
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer - Colonial
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Hospital System Dba The Center for Cancer Care
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic, PLLC
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, PA
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Omaha
country: United States
facility: Oncology Hematology West PC dba Nebraska Cancer Specialists
state: Nebraska
city: Lebanon
country: United States
facility: One Medical Center Drive
state: New Hampshire
city: Florham Park
country: United States
facility: Summit Medical Group, P.A.
state: New Jersey
city: New York
country: United States
facility: Clinical Research Alliance
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Springfield
country: United States
facility: Williamette Valley Cancer Center and Research Institute
state: Oregon
city: Watertown
country: United States
facility: Prairie Lakes Health Care System, Inc.
state: South Dakota
city: Germantown
country: United States
facility: Jones Clinic PC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Medical City Dallas
state: Texas
city: Fort Worth
country: United States
facility: Center for Cancer and Blood Disorders
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Network of South Texas
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Center of South Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, PC
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital North Star Lodge
state: Washington
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis-Jewish General Hospital
state: Quebec
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Sharman J, Hawkins M, Kolibaba K, Boxer M, Klein L, Wu M, Hu J, Abella S, Yasenchak C. An open-label phase 2 trial of entospletinib (GS-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2015 Apr 9;125(15):2336-43. doi: 10.1182/blood-2014-08-595934. Epub 2015 Feb 18.