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Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01796470
Recruitment Status : Completed
First Posted : February 21, 2013
Last Update Posted : January 23, 2017
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
This study will evaluate the efficacy, safety, tolerability, and pharmacodynamics of entospletinib and idelalisib. Participants will be enrolled who have one of the following hematological tumor types: chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or non-FL indolent non-Hodgkin lymphomas (iNHL; including lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia [LPL/WM], small lymphocytic lymphoma [SLL], or marginal zone lymphoma [MZL]).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Diffuse Large B-cell Lymphoma Indolent Non-Hodgkin's Lymphoma Drug: Entospletinib Drug: Idelalisib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Combination With Idelalisib in Subjects With Relapsed or Refractory Hematologic Malignancies
Study Start Date : June 2013
Actual Primary Completion Date : April 2014
Actual Study Completion Date : December 2016

Arm Intervention/treatment
Experimental: Entospletinib + idelalisib

Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg).

After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy.

Drug: Entospletinib
Entospletinib tablets administered orally twice daily
Other Name: GS-9973

Drug: Idelalisib
Idelalisib tablets administered orally twice daily
Other Names:
  • GS-1101
  • GS 1101
  • Cal-101
  • Cal 101
  • Zydelig®

Primary Outcome Measures :
  1. Objective response rate [ Time Frame: up to 48 weeks ]
    Objective response rate (ORR) as assessed by the Independent Review Committee (IRC), defined as the subjects' best overall response during entospletinib/idelalisib therapy and will include complete response (CR) or partial response (PR) (or very good partial response [VGPR] or minor response [MR] for subjects with LPL/WM)

Secondary Outcome Measures :
  1. Safety and tolerability [ Time Frame: up to 48 weeks ]
    Safety: laboratory data, adverse events (AEs), and treatment-emergent AEs will be collected. Safety will be assessed by grading of laboratory values and AEs according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  2. Maximum tolerated dose level [ Time Frame: up to 48 weeks ]
    Maximum tolerated dose level (MTD), defined as the highest dose level that was consistently well tolerated without dose limiting toxicity for the majority (ie, > 50%) of the subject's time on treatment as determined by the investigator for each subject

  3. Progression-free survival [ Time Frame: up to 48 weeks ]
    Progression-free survival (PFS), defined as the interval from the first dose of entospletinib/idelalisib to the earlier of the first documentation of definitive disease progression or death from any cause

  4. Duration of response [ Time Frame: up to 48 weeks ]
    Duration of response (DOR), defined as the interval from the time first response (CR or PR [or VGPR or MR for subjects with LPL/WM]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause

  5. Time to response [ Time Frame: up to 48 weeks ]
    Time to response (TTR), defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR [or VGPR or MR for subjects with LPL/WM]) is first achieved

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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®; GS-1101); subjects with malignancies being studied in these protocols must have failed screening and be registered as a screen failure in the respective idelalisib protocol
  • Prior treatment for lymphoid malignancy
  • Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
  • Discontinuation of all therapy for the treatment of cancer ≥ 3 weeks before the start of study drug
  • 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 NHL (ie, Richter transformation)
  • Known active central nervous system or leptomeningeal lymphoma
  • Presence of known intermediate- or high-grade myelodysplastic syndrome
  • Current therapy with agents that reduce gastric acidity, including but not limited to antacids, H2 inhibitors, and proton pump inhibitors
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01796470

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United States, California
Marin Cancer Care
Greenbrae, California, United States, 94904
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Pacific Shores Medical Group
Long Beach, California, United States, 90813
Ventura County Hematology Oncology Specialists
Oxnard, California, United States, 93030
Cancer Center of Santa Barbara
Santa Barbara, California, United States, 93105
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
Collaborative Research Group LLC
Boynton Beach, Florida, United States, 33435
United States, Kentucky
Montgomery Cancer Center
Mount Sterling, Kentucky, United States, 40353
United States, New York
New York University School of Medicine
New York, New York, United States, 10016
Weill Cornell Medical College
New York, New York, United States, 10021
University of Rochester, James P. Wilmot Cancer Center
Rochester, New York, United States, 14642
United States, Ohio
Signal Point Clinical Research Center, LLC
Middletown, Ohio, United States, 45042
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, South Carolina
Charleston Hematology Oncology
Charleston, South Carolina, United States, 29414
Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Utah Cancer Specialists
Salt Lake City, Utah, United States, 84106
United States, Washington
Northwest Medical Specialties
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Gilead Sciences
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Study Director: Gilead Study Director Gilead Sciences

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Gilead Sciences Identifier: NCT01796470     History of Changes
Other Study ID Numbers: GS-US-339-0103
First Posted: February 21, 2013    Key Record Dates
Last Update Posted: January 23, 2017
Last Verified: January 2017
Keywords provided by Gilead Sciences:
SYK inhibitor
PI3K inhibitor
GS 9973
GS 1101
Cal 101
Waldenström's macroglobulinemia
Additional relevant MeSH terms:
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Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, B-Cell
Lymphoma, B-Cell
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action