NCT01799889|TerminatedPhase 2ResultsDMCFDA Drug

Study Stopped

Sponsor's decision to discontinue development of entospletinib.

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

A Phase 2, Open-Label Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacodynamics of GS-9973 in Subjects With Relapsed or Refractory Hematologic Malignancies

Gilead Sciences ClinicalTrials.gov

Compare

1 other identifier

GS-US-339-0102

Study Type

interventional

Target

326

Locations

2 countries

Sites

Timeline

RegisteredFeb 2013

StartedMar 2013

CompletionJan 2020

Brief 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 \[MZL\]).

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

326

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Mar 2013

Longer than P75 for phase_2

Geographic Reach

2 countries

48 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.9 years study duration

First Submitted

Initial submission to the registry

February 13, 2013

Completed

14 days until next milestone

First Posted

Study publicly available on registry

February 27, 2013

Completed

15 days until next milestone

Study Start

First participant enrolled

March 14, 2013

Completed

4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 14, 2017

Completed

2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2020

Completed

8 months until next milestone

Results Posted

Study results publicly available

September 23, 2020

Completed

Last Updated

November 19, 2020

Status Verified

November 1, 2020

Enrollment Period

4.5 years

First QC Date

February 13, 2013

Results QC Date

September 2, 2020

Last Update Submit

November 2, 2020

Conditions

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

Keywords

SYK inhibitor

Outcome Measures

Primary Outcomes (2)

Progression-Free Survival (PFS) Rate of Participants With CLL After BCR Targeted Therapy, MCL, and DLBCL at Week 16
PFS rate was assessed by Independent Review Committee (IRC) and defined per standardized criteria (2007 Cheson criteria) (for NHL) and International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria (for CLL), as the percentage of participants not experiencing definitive progression or death. Disease progression was defined per standardized criteria as: evidence of any new disease; worsening of nodal or extra-nodal index lesions; unequivocal increase in the size of non-index lesions or non-measurable disease, size of the liver, spleen, or other organ; and a ≥ 25% increase from nadir in either monoclonal immunoglobulin M (IgM) concentration or total serum IgM quantitation. Disease progression was defined per standardized IWCLL criteria as: evidence of any new disease; worsening of index lesions, spleen or liver, or non-index disease; and decrease in platelet count or hemoglobin that is attributable to CLL. PFS rate was analyzed using Kaplan-Meier (KM) estimates.
Week 16
PFS Rate of Participants With CLL (Including CLL, Prior BCR Inhibitor Naive Participants), FL, and Non-FL iNHL at Week 24
PFS rate was assessed by IRC and defined per standardized criteria (2007 Cheson criteria) (for NHL) and IWCLL criteria (for CLL), as the percentage of participants not experiencing definitive progression or death. Disease progression was defined per standardized criteria (2007 Cheson criteria) as: evidence of any new disease; worsening of nodal or extra-nodal index lesions; unequivocal increase in the size of non-index lesions or non-measurable disease, size of the liver, spleen, or other organ; and a ≥ 25% increase from nadir in either monoclonal IgM concentration or total serum IgM quantitation. Disease progression was defined per standardized IWCLL criteria as: evidence of any new disease; worsening of index lesions, spleen or liver, or non-index disease; and decrease in platelet count or hemoglobin that is attributable to CLL. PFS rate was analyzed using KM estimates.
Week 24

Secondary Outcomes (6)

Percentage of Participants Experiencing Treatment-Emergent Adverse Events
First dose date up to the last dose date plus 30 days (maximum: 78.4 months)
Percentage of Participants With Hematology Postbaseline Toxicity Grade 3 or Higher
First dose date up to the last dose date plus 30 days (maximum: 78.4 months)
Percentage of Participants With Serum Chemistry Toxicity Postbaseline Grade 3 or Higher
First dose date up to the last dose date plus 30 days (maximum: 78.4 months)
Objective Response Rate (ORR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
From first dose date until first occurrence of CR or PR (or VGPR or MR for participants with LPL/WM) (up to approximately 7 years)
Duration of Response (DOR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
From the date of first documentation of CR or PR (or VGPR or MR for participants with LPL/WM) to disease progression or death from any cause (up to approximately 7 years)
+1 more secondary outcomes

Study Arms (12)

CLL, Entospletinib MM/SDD

EXPERIMENTAL

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.