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Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01799889
First Posted: February 27, 2013
Last Update Posted: June 19, 2017
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.
Information provided by (Responsible Party):
Gilead Sciences
  Purpose
This study will evaluate the efficacy, safety, tolerability, and pharmacodynamics of entospletinib. 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]).

Condition Intervention Phase
Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Diffuse Large B-cell Lymphoma Non-FL Indolent Non-Hodgkin's Lymphoma Follicular Lymphoma Drug: Entospletinib Drug: Entospletinib SDD Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel 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 Subjects With Relapsed or Refractory Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Up to 24 weeks ]
    Progression Free Survival (PFS) is defined as the interval from first dose of entospletinib to the earlier of the first documentation of definitive disease progression or death from any cause.


Secondary Outcome Measures:
  • Incidence of abnormal laboratory data and adverse events [ Time Frame: Up to 4 years ]
    This composite endpoint is to assess the safety and tolerability profile of entospletinib. Safety will be assessed by grading of laboratory values and adverse events according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  • Objective response rate [ Time Frame: Up to 4 years ]
    Objective response rate (ORR) will be determined from the participants' best response during entospletinib therapy and will include complete response (CR) and partial response (PR) (or very good partial response [VGPR] or minor response [MR] for subjects with LPL/WM).

  • Duration of response [ Time Frame: Up to 4 years ]
    Duration of response (DOR) is defined as time from the first response (CR or PR [or VGPR or MR for participants with LPL/WM]) is achieved until the earlier of the first documentation of definitive disease progression or death from any cause.

  • Time to response [ Time Frame: Up to 4 years ]
    Time to response (TTR) is defined as time from the first dose of entospletinib to the first time the response (CR or PR [or VGPR or MR for subjects with LPL/WM]) is achieved.


Enrollment: 326
Actual Study Start Date: March 14, 2013
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entospletinib LPL/WM, SLL, MZL
Participants with LPL/WM, SLL, and MZL will receive entospletinib 800 mg (Amendment 1-7) or 400 mg (Amendment 8 - spray-dried dispersion (SDD) tablet) twice daily.
Drug: Entospletinib
Tablet administered orally
Other Name: GS-9973
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib FL
Participants with FL will receive entospletinib 800 mg (Amendment 1-7) or 400 mg (Amendment 8 - SDD tablet) twice daily.
Drug: Entospletinib
Tablet administered orally
Other Name: GS-9973
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib DLBCL
Participants with DLBCL will receive entospletinib 800 mg (Amendment 1-7) or 400 mg (Amendment 8 - SDD tablet) twice daily.
Drug: Entospletinib
Tablet administered orally
Other Name: GS-9973
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib MCL
Participants with MCL will receive entospletinib 800 mg (Amendment 1-7) or 400 mg (Amendment 8 - SDD tablet) twice daily.
Drug: Entospletinib
Tablet administered orally
Other Name: GS-9973
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib CLL
Participants with CLL will receive entospletinib 800 mg (Amendment 1-7) or 400 mg (Amendment 8 - SDD tablet) twice daily.
Drug: Entospletinib
Tablet administered orally
Other Name: GS-9973
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib SDD CLL Prior BTK Exposure
Participants with CLL who have previously been treated with a bruton tyrosine kinase (BTK) inhibitor and now have progressive disease will receive entospletinib SDD 400 mg twice daily.
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib SDD CLL Prior PI3K Exposure
Participants with CLL who have previously been treated with a phosphatidylinositol 3-kinase (P13K) inhibitor and now have progressive disease will receive entospletinib SDD 400 mg twice daily.
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib SDD CLL Dose Ranging
Participants with CLL who are B-cell receptor (BCR) inhibitor treatment-naive will be randomized to receive 100, 200, or 400 mg of entospletinib SDD twice daily.
Drug: Entospletinib SDD
SDD tablet administered orally
Other Name: GS-9973 SDD

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 patient is enrolling in the B-cell receptor (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.

  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT01799889


  Show 48 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01799889     History of Changes
Other Study ID Numbers: GS-US-339-0102
First Submitted: February 13, 2013
First Posted: February 27, 2013
Last Update Posted: June 19, 2017
Last Verified: June 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:
GS-US-339-0102
SYK inhibitor
GS-9973
entospletinib
CLL
leukemia
lymphoma
MCL
DLBCL
iNHL
FL
MZL
LPL
SLL
WM
Waldenström's macroglobulinemia

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell