A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Subjects With Relapsed or Refractory Hematologic Malignancies
Status: Terminated
Location: See all (48) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
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
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:
• 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
Locations
United States
Alabama
University of Alabama at Birmingham
Birmingham
Arizona
Arizona Oncology Associates
Tucson
California
City of Hope National Medical Center
Duarte
Sharp Memorial Hospital
San Diego
Colorado
Rocky Mountain Cancer Centers, LLP
Boulder
Kaiser Permanente of Colorado
Denver
Connecticut
Cancer Center of Central Connecticut
Southington
Florida
Florida Cancer - Colonial
Fort Myers
Memorial Cancer Institute
Hollywood
Ocala Oncology Center
Ocala
Georgia
Northside Hospital
Atlanta
Gwinnett Hospital System Dba The Center for Cancer Care
Lawrenceville
Northwest Georgia Oncology Center
Marietta
Illinois
University of Chicago
Chicago
Illinois Cancer Specialists
Niles
Indiana
Indiana University Simon Cancer Center
Indianapolis
Louisiana
Hematology Oncology Clinic, PLLC
Baton Rouge
Massachusetts
Tufts Medical Center
Boston
Michigan
University of Michigan Health System
Ann Arbor
Karmanos Cancer Institute
Detroit
Minnesota
Minnesota Oncology Hematology, PA
Minneapolis
Mississippi
Hattiesburg Clinic
Hattiesburg
North Carolina
University of North Carolina
Chapel Hill
Nebraska
Oncology Hematology West PC dba Nebraska Cancer Specialists
Omaha
New Hampshire
One Medical Center Drive
Lebanon
New Jersey
Summit Medical Group, P.A.
Florham Park
New York
Clinical Research Alliance
New York
Ohio
Gabrail Cancer Center Research
Canton
Oncology Hematology Care
Cincinnati
Cleveland Clinic
Cleveland
Ohio State University Comprehensive Cancer Center
Columbus
Oregon
Williamette Valley Cancer Center and Research Institute
Springfield
South Dakota
Prairie Lakes Health Care System, Inc.
Watertown
Tennessee
Jones Clinic PC
Germantown
Tennessee Oncology, PLLC
Nashville
Texas
Texas Oncology-Austin Midtown
Austin
Texas Oncology-Medical City Dallas
Dallas
Center for Cancer and Blood Disorders
Fort Worth
Cancer Care Center of South Texas
San Antonio
Cancer Care Network of South Texas
San Antonio
Virginia
Virginia Cancer Specialists, PC
Fairfax
Virginia Cancer Institute
Richmond
Washington
Columbia Basin Hematology and Oncology
Kennewick
University of Washington
Seattle
Northwest Cancer Specialists, PC
Vancouver
Yakima Valley Memorial Hospital North Star Lodge
Yakima
Other Locations
Canada
Royal Victoria Regional Health Centre
Barrie
Sir Mortimer B. Davis-Jewish General Hospital
Montreal
Time Frame
Start Date: 2013-03-14
Completion Date: 2020-01-30
Participants
Target number of participants: 326
Treatments
Experimental: CLL, Entospletinib MM/SDD
Participants with CLL, receive original formulation (mono-mesylate \[MM\]) of entospletinib 800 mg (4 × 200 mg tablets) (before amendment 8) or new formulation of entospletinib (spray dried dispersion \[SDD\]) 400 mg (2 × 200 mg tablets) (after amendment 8) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: FL, Entospletinib MM/SDD
Participants with FL, receive original formulation of entospletinib 800 mg (4 × 200 mg tablets) (before amendment 8) or new formulation of entospletinib 400 mg (2 × 200 mg tablets) (after amendment 8) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: DLBCL, Entospletinib MM/SDD
Participants with DLBCL, receive original formulation of entospletinib 800 mg (4 × 200 mg tablets) (before amendment 8) or new formulation of entospletinib 400 mg (2 × 200 mg tablets) (after amendment 8) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: MCL, Entospletinib MM/SDD
Participants with MCL, receive original formulation of entospletinib 800 mg (4 × 200 mg tablets) (before amendment 8) or new formulation of entospletinib 400 mg (2 × 200 mg tablets) (after amendment 8) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: non-FL iNHL, Entospletinib MM/SDD
Participants with non-FL iNHL (ie, participants with LPL/WM, SLL, or MZL), receive original formulation of entospletinib 800 mg (4 × 200 mg tablets) (before amendment 8) or new formulation of entospletinib 400 mg (2 × 200 mg tablets) (after amendment 8) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 100 mg
Participants with CLL, who are prior B-cell receptor (BCR) inhibitor naive, receive new formulation of entospletinib 100 mg (1 × 100 mg tablet) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 200 mg
Participants with CLL, who are prior BCR inhibitor naive, receive new formulation of entospletinib 200 mg (1 × 200 mg tablet) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 400 mg
Participants with CLL, who are prior BCR inhibitor naive, receive new formulation of entospletinib 400 mg (2 × 200 mg tablets) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL (Non-Richters) Prior BTK Inhibitor, Entospletinib SDD
Participants with CLL and simple progression (non-Richters), who are exposed to Bruton tyrosine kinase (BTK) inhibitor, receive new formulation of entospletinib 400 mg (2 × 200 mg tablets) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL (Non-Richters) Prior PI3K Inhibitor, Entospletinib SDD
Participants with CLL and simple progression (non-Richters), who are exposed to phosphatidylinositol 3-kinase (PI3K) inhibitor, receive new formulation of entospletinib 400 mg (2 × 200 mg tablets) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL (Richters) Prior BTK Inhibitor, Entospletinib SDD
Participants with CLL, who transform to Richters or Richters-like syndrome and are exposed to BTK inhibitor, receive new formulation of entospletinib 400 mg (2 × 200 mg tablets) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Experimental: CLL (Richters) Prior PI3K Inhibitor, Entospletinib SDD
Participants with CLL, who transform to Richters or Richters-like syndrome and are exposed to PI3K inhibitor, receive new formulation of entospletinib 400 mg (2 × 200 mg tablets) orally twice daily. Treatment with entospletinib will continue until disease progression or unacceptable toxicity.
Authors
Mitchell Smith, Andrei Shustov, James Khatcheressian, Stefano Tarantolo, Caroline Behler, Dean Kirkel, Ian Flinn, Kathryn Kolibaba, Thomas Giever, Ramakrishna Battini, Alfred Saleh, Dipti Patel-Donnelly, Andreas Klein, Timothy Wassenaar, Farrukh Awan, Bruce Bank, Leonard Klein, Michael Thirman, Roger Lyons, Morton Coleman, David Andorsky, Jay Courtright, Jose Azar, Clyde Jones, Frederick Lansigan, Charles Farber, Andres Forero-Torres, Christopher Hagenstad, Steven Park, Catherine Coombs, Muthalagu Ramanathan, Richard Frank, Lowell Hart, Rama Balaraman, Robert Chen, Allyson Harroff, Patrick Flynn, Sarit Assouline
Related Therapeutic Areas
Sponsors
Leads: Gilead Sciences