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Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies

NCT ID: NCT01799889

Last Updated: 2020-11-19

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

326 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-14

Study Completion Date

2020-01-30

Brief Summary

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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 \[MZL\]).

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Diffuse Large B-cell Lymphoma Non-FL Indolent Non-Hodgkin's Lymphoma Follicular Lymphoma

Keywords

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SYK inhibitor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Entospletinib MM

Intervention Type DRUG

Entospletinib MM tablet administered orally

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib MM

Intervention Type DRUG

Entospletinib MM tablet administered orally

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib MM

Intervention Type DRUG

Entospletinib MM tablet administered orally

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib MM

Intervention Type DRUG

Entospletinib MM tablet administered orally

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib MM

Intervention Type DRUG

Entospletinib MM tablet administered orally

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

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.

Group Type EXPERIMENTAL

Entospletinib SDD

Intervention Type DRUG

Entospletinib SDD tablet administered orally

Interventions

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Entospletinib MM

Entospletinib MM tablet administered orally

Intervention Type DRUG

Entospletinib SDD

Entospletinib SDD tablet administered orally

Intervention Type DRUG

Other Intervention Names

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GS-9973 GS-9973 SDD

Eligibility Criteria

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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 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Arizona Oncology Associates

Tucson, Arizona, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Rocky Mountain Cancer Centers, LLP

Boulder, Colorado, United States

Site Status

Kaiser Permanente of Colorado

Denver, Colorado, United States

Site Status

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Site Status

Florida Cancer - Colonial

Fort Myers, Florida, United States

Site Status

Memorial Cancer Institute

Hollywood, Florida, United States

Site Status

Ocala Oncology Center

Ocala, Florida, United States

Site Status

Northside Hospital

Atlanta, Georgia, United States

Site Status

Gwinnett Hospital System Dba The Center for Cancer Care

Lawrenceville, Georgia, United States

Site Status

Northwest Georgia Oncology Center

Marietta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Illinois Cancer Specialists

Niles, Illinois, United States

Site Status

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Hematology Oncology Clinic, PLLC

Baton Rouge, Louisiana, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Health System

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Minnesota Oncology Hematology, PA

Minneapolis, Minnesota, United States

Site Status

Hattiesburg Clinic

Hattiesburg, Mississippi, United States

Site Status

Oncology Hematology West PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

One Medical Center Drive

Lebanon, New Hampshire, United States

Site Status

Summit Medical Group, P.A.

Florham Park, New Jersey, United States

Site Status

Clinical Research Alliance

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status

Oncology Hematology Care

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Williamette Valley Cancer Center and Research Institute

Springfield, Oregon, United States

Site Status

Prairie Lakes Health Care System, Inc.

Watertown, South Dakota, United States

Site Status

Jones Clinic PC

Germantown, Tennessee, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Texas Oncology-Austin Midtown

Austin, Texas, United States

Site Status

Texas Oncology-Medical City Dallas

Dallas, Texas, United States

Site Status

Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Site Status

Cancer Care Network of South Texas

San Antonio, Texas, United States

Site Status

Cancer Care Center of South Texas

San Antonio, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Virginia Cancer Institute

Richmond, Virginia, United States

Site Status

Columbia Basin Hematology and Oncology

Kennewick, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Northwest Cancer Specialists, PC

Vancouver, Washington, United States

Site Status

Yakima Valley Memorial Hospital North Star Lodge

Yakima, Washington, United States

Site Status

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

Site Status

Sir Mortimer B. Davis-Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 25696919 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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GS-US-339-0102

Identifier Type: -

Identifier Source: org_study_id