Chronic Lymphocytic LeukemiaPhase 2NCT01799889
Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies
A Phase 2 study testing Entospletinib MM and Entospletinib SDD in people with Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma, run by Gilead Sciences at 48 sites in 2 countries.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma
- What is being tested?
- Entospletinib MM and Entospletinib SDD
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 326 participants
- Where
- 48 sitesin 2 countries
- Study dates
- 14 Mar 2013to 30 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
48 sites in 2 countries.
48 sites in 2 countries
United States46 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Northside Hospital
Atlanta, Georgia, 30341
Texas Oncology-Austin Midtown
Austin, Texas, 78705
Hematology Oncology Clinic, PLLC
Baton Rouge, Louisiana, 70809
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Tufts Medical Center
Boston, Massachusetts, 02111
Rocky Mountain Cancer Centers, LLP
Boulder, Colorado, 80303
Gabrail Cancer Center Research
Canton, Ohio, 44718
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Chicago
Chicago, Illinois, 60637
Oncology Hematology Care
Cincinnati, Ohio, 45242
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Texas Oncology-Medical City Dallas
Dallas, Texas, 75230
Kaiser Permanente of Colorado
Denver, Colorado, 80218
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope National Medical Center
Duarte, California, 91010
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Summit Medical Group, P.A.
Florham Park, New Jersey, 07932
Florida Cancer - Colonial
Fort Myers, Florida, 33905
Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Jones Clinic PC
Germantown, Tennessee, 38138
Hattiesburg Clinic
Hattiesburg, Mississippi, 39401
Memorial Cancer Institute
Hollywood, Florida, 33021
Indiana University Simon Cancer Center
Indianapolis, Indiana, 46202
Columbia Basin Hematology and Oncology
Kennewick, Washington, 99336
Gwinnett Hospital System Dba The Center for Cancer Care
Lawrenceville, Georgia, 30046
One Medical Center Drive
Lebanon, New Hampshire, 03756
Northwest Georgia Oncology Center
Marietta, Georgia, 30060
Minnesota Oncology Hematology, PA
Minneapolis, Minnesota, 55404
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Clinical Research Alliance
New York, New York, 10021
Illinois Cancer Specialists
Niles, Illinois, 60714
Ocala Oncology Center
Ocala, Florida, 34471
Oncology Hematology West PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Virginia Cancer Institute
Richmond, Virginia, 23226
Cancer Care Network of South Texas
San Antonio, Texas, 78217
Cancer Care Center of South Texas
San Antonio, Texas, 78229
Sharp Memorial Hospital
San Diego, California, 92123
University of Washington
Seattle, Washington, 98109
Cancer Center of Central Connecticut
Southington, Connecticut, 06489
Williamette Valley Cancer Center and Research Institute
Springfield, Oregon, 97477
Arizona Oncology Associates
Tucson, Arizona, 85710
Northwest Cancer Specialists, PC
Vancouver, Washington, 98684
Prairie Lakes Health Care System, Inc.
Watertown, South Dakota, 57201
Yakima Valley Memorial Hospital North Star Lodge
Yakima, Washington, 98902
Canada2 sites
Royal Victoria Regional Health Centre
Barrie, Ontario, L4M 6M2
Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec, H3T 1E2
About this study
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
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]).
- Conditions
- Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma, Non-FL Indolent Non-Hodgkin's Lymphoma, Follicular Lymphoma
- Being tested
- Entospletinib MM, Entospletinib SDD
- Keywords
- SYK inhibitor
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Entospletinib MMDrug
Also called GS-9973
Entospletinib MM tablet administered orally
Entospletinib SDDDrug
Also called GS-9973 SDD
Entospletinib SDD tablet administered orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Entospletinib MM; Drug: Entospletinib SDD |
| FL, Entospletinib MM/SDD | Experimental | 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. Receives: Drug: Entospletinib MM; Drug: Entospletinib SDD |
| DLBCL, Entospletinib MM/SDD | Experimental | 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. Receives: Drug: Entospletinib MM; Drug: Entospletinib SDD |
| MCL, Entospletinib MM/SDD | Experimental | 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. Receives: Drug: Entospletinib MM; Drug: Entospletinib SDD |
| non-FL iNHL, Entospletinib MM/SDD | Experimental | 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. Receives: Drug: Entospletinib MM; Drug: Entospletinib SDD |
| CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 100 mg | Experimental | 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. Receives: Drug: Entospletinib SDD |
| CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 200 mg | Experimental | 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. Receives: Drug: Entospletinib SDD |
| CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 400 mg | Experimental | 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. Receives: Drug: Entospletinib SDD |
| CLL (Non-Richters) Prior BTK Inhibitor, Entospletinib SDD | Experimental | 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. Receives: Drug: Entospletinib SDD |
| CLL (Non-Richters) Prior PI3K Inhibitor, Entospletinib SDD | Experimental | 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. Receives: Drug: Entospletinib SDD |
| CLL (Richters) Prior BTK Inhibitor, Entospletinib SDD | Experimental | 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. Receives: Drug: Entospletinib SDD |
| CLL (Richters) Prior PI3K Inhibitor, Entospletinib SDD | Experimental | 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. Receives: Drug: Entospletinib SDD |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Week 24
Secondary outcomes (6)
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
A treatment-emergent Adverse Event (AE) was defined as an AE that occurs in the period from the first dose of study treatment to 30 days after the last dose of study treatment or leads to discontinuation of study treatment. Participants were assessed for AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Measured: 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
Hematology toxicity at any time postbaseline was summarized according to the NCI CTCAE, version 4.03. The most severe graded abnormality was counted for each participant per test.
ANC = absolute neutrophil count; Hb = hemoglobin; WBC = white blood cells
Measured: 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
Serum chemistry toxicity at anytime postbaseline was summarized according to the NCI CTCAE, version 4.03. The most severe graded abnormality was counted for each participant per test. ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase
Measured: 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)
ORR: percentage of participants with complete response (CR) or partial response (PR) (or very good PR [VGPR] or minor response [MR] for participants with LPL/WM). Per 2007 Cheson criteria, CR: complete resolution of all disease-related radiological abnormalities; PR: ≥50% reduction in sum of products (SPD) of the longest diameters of all index lesions, no new lesions; VGPR: >90% decrease from baseline (DFB) in IgM, and other criteria for CR met; MR: ≥25% but <50% DFB in IgM, no increase from baseline (IFB) in SPD of lesions, no new lesions. Per IWCLL, CR: lymphocytes (Ly) <4*10^9/L, no lymphadenopathy, normal spleen and liver size, absence of disease, absolute neutrophil count (ANC) >1.5*10^9/L, platelets ≥100*10^9/L, hemoglobin (Hb) >110 g/L, bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy, size of liver and spleen, bone marrow infiltrates; and ≥1 of these: ANC >1500/μL, platelets ≥100,000/µL, Hb >11 g/dL.
Measured: 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)
DOR was defined as the interval from first documentation of CR or PR (or VGPR or MR for participants with LPL/WM) to earlier of first documentation of definitive disease progression or death from any cause. Per 2007 Cheson criteria, CR: complete resolution of all disease-related radiological abnormalities; PR: ≥50% reduction in SPD of longest diameters of all index lesions, no new lesions; VGPR: >90% DFB in IgM, and other criteria for CR met; MR: ≥25% but <50% DFB in IgM, no IFB in SPD of lesions, no new lesions. Per IWCLL criteria, CR: Ly <4*10^9/L, no lymphadenopathy, normal spleen and liver size, absence of disease, ANC >1.5*10^9/L, platelets ≥100*10^9/L, Hb >110 g/L, bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy, size of liver and spleen, bone marrow infiltrates; and ≥1 of these: ANC>1500/μL, platelets ≥100,000/µL, Hb >11 g/dL. Disease progression: as defined in Outcome measure 1. DOR was analyzed using KM estimates.
Measured: 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)
Time to Response (TTR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
TTR was defined as the interval from the first dose of study drug to the first documentation of CR or PR (or VGPR or MR for participants with LPL/WM). Per 2007 Cheson criteria, CR: complete resolution of all disease-related radiological abnormalities; PR: ≥ 50% reduction in SPD of the longest diameters of all index lesions, no new lesions; VGPR: >90% DFB in IgM, and other criteria for CR met; MR: ≥25% but <50% DFB in IgM, no IFB in SPD of lesions, no new lesions. Per IWCLL criteria, CR: Ly <4*10^9/L, no lymphadenopathy, normal spleen and liver size, absence of disease, ANC >1.5*10^9/L, platelets ≥100*10^9/L, Hb >110 g/L, bone marrow at least normocellular for age; PR: ≥2 of these: ≥50% decrease in Ly, lymphadenopathy, size of liver and spleen, bone marrow infiltrates; and ≥1 of these: ANC >1500/μL, platelets ≥100,000/µL, Hb >11 g/dL.
Measured: From the first dose of study drug to the first documentation of CR or PR (or VGPR or MR for participants with LPL/WM) (up to approximately 7 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2013 (estimated)
- Study start14 Mar 2013
- Primary completion14 Sep 2017
- Study completion30 Jan 2020
Why it stopped: Sponsor's decision to discontinue development of entospletinib.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 326 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01799889
- Sponsor's protocol ID
- GS-US-339-0102
- Status last verified
- Nov 2020
- First submitted
- 13 Feb 2013
- Last updated
- 19 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25696919
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01799889
- Acronym / sponsor ID
- GS-US-339-0102
- Conditions
- Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Diffuse Large B-cell Lymphoma, Non-FL Indolent Non-Hodgkin's Lymphoma, Follicular Lymphoma
- Keywords
- SYK inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision to discontinue development of entospletinib.
- Enrolment
- 326 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 14 Mar 2013 (actual)
- Primary completion
- 14 Sep 2017 (actual)
- Study completion
- 30 Jan 2020 (actual)
- First posted
- 27 Feb 2013 (estimated)
- Results
- Posted 23 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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]).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
| Arm | Type | Receives |
|---|---|---|
| CLL, Entospletinib MM/SDD | Experimental | Drug: Entospletinib MM, Drug: Entospletinib SDDParticipants 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. |
| FL, Entospletinib MM/SDD | Experimental | Drug: Entospletinib MM, Drug: Entospletinib SDDParticipants 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. |
| DLBCL, Entospletinib MM/SDD | Experimental | Drug: Entospletinib MM, Drug: Entospletinib SDDParticipants 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. |
| MCL, Entospletinib MM/SDD | Experimental | Drug: Entospletinib MM, Drug: Entospletinib SDDParticipants 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. |
| non-FL iNHL, Entospletinib MM/SDD | Experimental | Drug: Entospletinib MM, Drug: Entospletinib SDDParticipants 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. |
| CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 100 mg | Experimental | Drug: Entospletinib SDDParticipants 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. |
| CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 200 mg | Experimental | Drug: Entospletinib SDDParticipants 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. |
| CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 400 mg | Experimental | Drug: Entospletinib SDDParticipants 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. |
| CLL (Non-Richters) Prior BTK Inhibitor, Entospletinib SDD | Experimental | Drug: Entospletinib SDDParticipants 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. |
| CLL (Non-Richters) Prior PI3K Inhibitor, Entospletinib SDD | Experimental | Drug: Entospletinib SDDParticipants 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. |
| CLL (Richters) Prior BTK Inhibitor, Entospletinib SDD | Experimental | Drug: Entospletinib SDDParticipants 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. |
| CLL (Richters) Prior PI3K Inhibitor, Entospletinib SDD | Experimental | Drug: Entospletinib SDDParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Entospletinib MMAlso: GS-9973Entospletinib MM tablet administered orally | Drug | CLL, Entospletinib MM/SDD, DLBCL, Entospletinib MM/SDD, FL, Entospletinib MM/SDD, MCL, Entospletinib MM/SDD, non-FL iNHL, Entospletinib MM/SDD |
| Entospletinib SDDAlso: GS-9973 SDDEntospletinib SDD tablet administered orally | Drug | CLL (Non-Richters) Prior BTK Inhibitor, Entospletinib SDD, CLL (Non-Richters) Prior PI3K Inhibitor, Entospletinib SDD, CLL (Richters) Prior BTK Inhibitor, Entospletinib SDD, CLL (Richters) Prior PI3K Inhibitor, Entospletinib SDD, CLL, Entospletinib MM/SDD, CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 100 mg, CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 200 mg, CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 400 mg, DLBCL, Entospletinib MM/SDD, FL, Entospletinib MM/SDD, MCL, Entospletinib MM/SDD, non-FL iNHL, Entospletinib MM/SDD |
Primary outcome
Progression-Free Survival (PFS) Rate of Participants With CLL After BCR Targeted Therapy, MCL, and DLBCL at Week 16
Time frame: 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.
PFS Rate of Participants With CLL (Including CLL, Prior BCR Inhibitor Naive Participants), FL, and Non-FL iNHL at Week 24
Time frame: 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.
6 secondary outcomes
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time to Response (TTR), as Assessed by IRC Per Standardized Criteria (2007 Cheson Criteria) (for NHL) and IWCLL Criteria (for CLL)
Time frame: From the first dose of study drug to the first documentation of CR or PR (or VGPR or MR for participants with LPL/WM) (up to approximately 7 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25696919Sharman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
48 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entospletinib MM and Entospletinib SDD in people with Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma, run by Gilead Sciences at 48 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) Rate of Participants With CLL After BCR Targeted Therapy, MCL, and DLBCL at Week 16 (time frame: Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01799889, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020.