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Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01799889
First received: February 13, 2013
Last updated: August 23, 2016
Last verified: August 2016
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 385
Study Start Date: March 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 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 twice daily.
Drug: Entospletinib
Entospletinib tablet administered orally
Other Name: GS-9973
Experimental: Entospletinib FL
Participants with FL will receive entospletinib 800 mg twice daily.
Drug: Entospletinib
Entospletinib tablet administered orally
Other Name: GS-9973
Experimental: Entospletinib DLBCL
Participants with DLBCL will receive entospletinib 800 mg twice daily.
Drug: Entospletinib
Entospletinib tablet administered orally
Other Name: GS-9973
Experimental: Entospletinib MCL
Participants with MCL will receive entospletinib 800 mg twice daily.
Drug: Entospletinib
Entospletinib tablet administered orally
Other Name: GS-9973
Experimental: Entospletinib CLL
Participants with CLL will receive entospletinib 800 mg twice daily.
Drug: Entospletinib
Entospletinib tablet administered orally
Other Name: GS-9973
Experimental: Entospletinib SDD CLL Prior BTK Exposure
Participants with CLL who have previously been treated with a bruton tyrosine kinase (BTK) and now have progressive disease will receive entospletinib SDD 400 mg twice daily.
Drug: Entospletinib SDD
Entospletinib spray-dried dispersion (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) and now have progressive disease will receive entospletinib SDD 400 mg twice daily.
Drug: Entospletinib SDD
Entospletinib spray-dried dispersion (SDD) tablet administered orally
Other Name: GS-9973 SDD
Experimental: Entospletinib SDD CLL Dose Ranging
Participants with CLL who are B-cell receptor (BCR) treatment-naive will be randomized to receive 100, 200, or 400 mg of entospletinib SDD twice daily.
Drug: Entospletinib SDD
Entospletinib spray-dried dispersion (SDD) tablet administered orally
Other Name: GS-9973 SDD

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01799889

Contacts
Contact: Gilead Study Team GS9973alerts@gilead.com

  Show 65 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Steve Abella, M.D. 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 
Study First Received: February 13, 2013
Last Updated: August 23, 2016
Health Authority: United States: Food and Drug Administration

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, Follicular
Lymphoma
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

ClinicalTrials.gov processed this record on September 23, 2016