Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Waldenstrom Macroglobulinemia

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Chronic Lymphocytic Leukemia

Follicular Lymphoma

Marginal Zone Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Idelalisib

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Participants will receive rituximab + bendamustine + idelalisib.

Participants will receive rituximab + bendamustine + placebo.

150 mg tablet administered orally twice daily

375 mg/m\^2 single-use vials administered intravenously every 4 weeks (up to a total of 6 infusions)

90 mg/m\^2 single-use vials administered intravenously for two consecutive days every 4 weeks (up to a total of 4-6 cycles as tolerated)

Bendamustine

Placebo

Gilead Study Director

The primary objective of this study is to evaluate the addition of idelalisib to bendamustine/rituximab on progression-free survival (PFS) in adults with previously treated indolent non-Hodgkin lymphoma (iNHL).

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line iNHL treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.

PFS is defined as the interval from randomization to the earlier of the first documentation of definitive indolent non-Hodgkin lymphomas (iNHL) disease progression or death from any cause. Definitive iNHL disease progression is progression based on standard criteria. PFS was to be assessed by an independent review committee (IRC).

Complete response rate is defined as the proportion of participants who achieve a complete response. CR rate was to be assessed by an IRC.

Overall response rate is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response (VGPR) or minor response (MR) for participants with Waldenstrom's). ORR was to be assessed by an IRC.

Lymph node response rate is defined as the proportion of participants who achieve ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Lymph node response rate was to be assessed by an IRC.

Overall survival is defined as the interval from randomization to death from any cause.

Gilead Sciences

Safety Analysis Set: all participants who took at least 1 dose of study drug

Idelalisib 150 mg tablet twice daily + bendamustine intravenously (starting dose of 90 mg/m\^2 for up to 12 infusions) + rituximab intravenously (375 mg/m\^2 on Day 1 for a total of 6 infusions)

Idelalisib + Bendamustine + Rituximab

Placebo tablet twice daily + bendamustine intravenously (starting dose of 90 mg/m\^2 for up to 12 infusions) + rituximab intravenously (375 mg/m\^2 on Day 1 for a total of 6 infusions)

Placebo + Bendamustine + Rituximab

Total

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Other

Not Permitted

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Russian Federation

United States

United Kingdom

Spain

Canada

Czech Republic

Sweden

Taiwan

Poland

Korea, Republic of

Italy

Israel

France

Australia

Germany

Region of Enrollment

The Intent to Treat (ITT) Analysis Set: all participants who were randomized regardless of whether they received any study treatment

Due to the early termination of the study, efficacy data were not available for all participants, and therefore the prespecified analyses were not conducted.

Clinical Trial Disclosures

Progression-free Survival (PFS)

Complete Response Rate (CR)

Overall Response Rate (ORR)

Lymph Node Response Rate

Due to the early termination of the study, efficacy data were not mature for all participants, and therefore the prespecified analyses were not conducted.

Overall Survival (OS)

Idelalisib (Zydelig®) 150 mg tablet twice daily + bendamustine intravenously (starting dose of 90 mg/m\^2 for up to 12 infusions)

+ rituximab intravenously (375 mg/m\^2 on Day 1 for a total of 6 infusions)

Overall Study

Participants will receive rituximab + idelalisib.

Participants will receive rituximab + placebo. Following confirmation of iNHL disease progression by the independent review committee and unblinding, participants may be eligible to receive open-label idelalisib 150 mg twice daily.

375 mg/m\^2 administered intravenously weekly for 4 weeks, then every 8 weeks (up to a total of 8 infusions)

150 mg tablets administered orally twice daily

The primary objective of this study is to evaluate the effect of the addition of idelalisib to rituximab on progression-free survival (PFS) in adults with previously treated indolent non-Hodgkin lymphoma (iNHL).

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line chronic lymphocytic leukemia (CLL) and early-line iNHL treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated this study in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA).

Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas

Progression-free survival (PFS) is defined as the interval from randomization to the earlier of the first documentation of definitive indolent non-Hodgkin lymphoma (iNHL) disease progression or death from any cause. PFS was to be assessed by an independent review committee (IRC).

Overall Response Rate (ORR) is defined as the proportion of participants who achieve a complete response or partial response (or very good partial response or minor response for participants with Waldenstrom's). ORR was to be assessed by an IRC.

Complete response rate is defined as the proportion of participants who achieve a complete response. Complete response rate was to be assessed by an IRC.

Idelalisib 150 mg tablet orally twice daily + rituximab 375 mg/m\^2 intravenously starting on Day 1 for a total of 8 infusions

Idelalisib + Rituximab

Placebo tablet orally twice daily + rituximab 375 mg/m\^2 intravenously starting on Day 1 for a total of 8 infusions

Placebo + Rituximab

Unknown or Not Reported

Singapore

Romania

Hungary

Japan

Portugal

Intent-to-Treat (ITT) Analysis Set: all participants who were randomized regardless of whether they received any study treatment

Progression Free Survival

Overall Response Rate

Complete Response Rate

Overall Survival

Idelalisib (Zydelig®) 150 mg tablet orally twice daily + rituximab 375 mg/m\^2 intravenously starting on Day 1 for a total of 8 infusions

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Leukemia

Leukemia, Lymphoid

Lymphoma, Mantle-Cell

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Chronic Graft Versus Host Disease

Mantle Cell Lymphoma

200 mg twice daily (with possible dose reduction to 100 mg twice daily)

Patients will receive continuous treatment until progressive disease, toxicity, or until any other condition for treatment discontinuation has been met.

Pacritinib

Ryan Wilcox, MD, PhD

This trial will determine the safety and tolerability of Pacritinib in patients with relapsed/refractory lymphoproliferative disorders.

Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

Phase Ib, Open Label, Single Center Study of Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders

Dose limiting toxicity (DLT) rate during the 1st cycle (28 days) of pacritinib.

Overall response rate (ORR), defined as best disease response recorded from first day of treatment until disease progression or initiation of new antineoplastic therapy.

Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.

Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.

DOR, defined as time from documented remission to the time of death, relapse, or initiation of alternative antineoplastic.

Responses for patients with NHL or small lymphocytic lymphoma will be performed in accordance with the Revised Lugano classification staging system for non-Hodgkin's Lymphoma. Responses for patients with CLL will be evaluated in accordance with criteria of the International Workshop on Chronic Lymphocytic Leukemia, with the exception that lymphocytosis will not be the sole criteria for disease progression. Responses for CTCL will be assessed by the modified Severity Weighted Assessment Tool, response in blood, nodes, viscera, and the global composite scoring system.

Time to next treatment, defined as time from first dose of pacritinib to initiation of alternative antineoplastic therapy

University of Michigan Rogel Cancer Center

Lymphoma, Large B-Cell, Diffuse

Hematologic Neoplasms

Lymphoma, B-Cell

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg).

After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy.

Entospletinib tablets administered orally twice daily

Entospletinib

Idelalisib tablets administered orally twice daily

This study will evaluate the efficacy of the combination entospletinib and idelalisib in participants with relapsed or refractory hematologic malignancies. Participants will be enrolled who have one of the following hematological tumor types: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or indolent non-Hodgkin lymphomas (iNHL; including follicular lymphoma (FL) and lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia \[LPL/WM\], small lymphocytic lymphoma \[SLL\], or marginal zone lymphoma \[MZL\]).

Entospletinib in Combination With Idelalisib 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 Combination With Idelalisib in Subjects With Relapsed or Refractory Hematologic Malignancies

ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response \[VGPR\] or minor response \[MR\] for participants with LPL/WM). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively.

A treatment-emergent Adverse Event (AE) was defined as any AE with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drugs or an AE leading to premature discontinuation of study drug. An AE is any untoward medical occurrence in a clinical investigation where participants administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.

A treatment-emergent laboratory (Hematology, Serum Chemistry and Urinalysis) abnormality was defined as an abnormality that, compared to baseline, worsens by ≥ 1 grade in the period from the first dose of study drug. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening or disabling. If baseline data are missing, then any graded abnormality (i.e., an abnormality that is Grade ≥ 1 in severity) will be considered treatment-emergent. The percentage of participants in each worst postbaseline grade is reported.

Maximum tolerated dose (MTD) is defined as the highest dose level that was consistently well tolerated without dose limiting toxicity (DLT) for the majority of participants time on treatment (ie,\> 50%) as determined by the investigator for each participant. DLTs are defined as Grade 4 hematological toxicities persisting for ≥ 14 days or Grade ≥ 3 toxicities of other types.

PFS was defined as the interval from the first dose of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.

DOR was defined as the interval from the first-time response (CR or PR \[or VGPR or MR for participants with LPL/WM\]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.

TTR was defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR \[or VGPR or MR for participants with LPL/WM\]) is first achieved. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.

The Safety Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).

Participants with a documented diagnosis of chronic lymphocytic leukemia (CLL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Entospletinib + Idelalisib CLL

Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Entospletinib + Idelalisib iNHL: FL

Participants with a documented diagnosis of diffuse large B-cell lymphoma (DLBCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred ,increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Entospletinib + Idelalisib DLBCL

Participants with a documented diagnosis of mantle cell lymphoma (MCL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred, increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Entospletinib + Idelalisib MCL

Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL), and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Entospletinib + Idelalisib iNHL: Others

Participants with a documented diagnosis of indolent non-Hodgkin lymphoma (iNHL) with follicular lymphoma (FL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) occurred, increased dose to 600 mg/100 mg for 2 weeks, if no DLT occurred, increased dose to 800 mg/100 mg for 4 weeks, if no DLT occurred increased dose to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months

Participants with a documented diagnosis of iNHL with other subtypes lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) were included in this arm. Participants were administered 4 dose combinations of entospletinib plus idelalisib tablets orally twice daily under fasted conditions (400 mg/100 mg for 2 weeks, if no dose limiting toxicity (DLT) increased to 600 mg/100 mg for 2 weeks, if no DLT increased to 800 mg/100 mg for 4 weeks, if no DLT increased to 800 mg/150 mg) for up to 6 months. After discontinuation of combination therapy and a washout period of 14-28 days, participants could continue to receive entospletinib 400 mg monotherapy for up to 18 months.

Ethnicity

Not Permitted Category used, as local regulators did not allow collection of race or ethnicity information.

Race

Karnofsky Performance Status will be assessed on a scale of 0-100 where 0 indicates death and 100 indicates normal activity.

Karnofsky Performance Status

The Full Analysis Set comprised all participants who received ≥ 1 dose of study drug (entospletinib or idelalisib).

As a result of the early termination of the trial for safety, the efficacy endpoints were not evaluable due to insufficient treatment exposure.

Gilead Clinical Study Information Center

The study was terminated due to safety measures. Complete data was not collected for any participant.

Objective Response Rate (ORR)

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Neutrophils Count Decreased (Grade 1)

Neutrophils Count Decreased (Grade 2)

Neutrophils Count Decreased (Grade 3)

Neutrophils Count Decreased (Grade 4)

Anemia (Grade 1)

Anemia (Grade 2)

Anemia (Grade 3)

Participants in the Safety Analysis Set were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Idelalisib (GS-1101) in Combination With Bendamustine and Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas	NCT01732926	Indolent Non-Ho...	Idelalisib Rituximab Bendamustine Placebo	18 Years -	Gilead Sciences
Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Indolent Non-Hodgkin Lymphomas	NCT01732913	Indolent Non-Ho...	Placebo Rituximab Idelalisib	18 Years -	Gilead Sciences
Pacritinib in Relapsed/Refractory Lymphoproliferative Disorders	NCT03601819	Lymphoma, T-Cel... Lymphoma, T-Cel... Chronic Lymphoc... Lymphoprolifera... Waldenstrom Mac... Lymphoplasmacyt... Mantle Cell Lym...	Pacritinib	18 Years -	University of Michigan Rogel Cancer Center
Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies	NCT01796470	Chronic Lymphoc... Mantle Cell Lym... Diffuse Large B... Indolent Non-Ho...	Entospletinib Idelalisib	18 Years -	Gilead Sciences
Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies	NCT01796470	Chronic Lymphoc... Mantle Cell Lym... Diffuse Large B... Indolent Non-Ho...	Entospletinib Idelalisib	18 Years -	Gilead Sciences
Trial to Evaluate the Safety and Pharmacokinetics of HMPL-689 in Patients With Lymphomas	NCT03786926	Lymphoma	HMPL-689	18 Years -	Hutchmed
A Study of CG-806 in Patients With Relapsed or Refractory CLL/SLL or Non-Hodgkin's Lymphomas	NCT03893682	Chronic Lymphoc... Small Lymphocyt... Non-Hodgkin's L...	CG-806	18 Years -	Aptose Biosciences Inc.

Spots Global Cancer Trial Database for lpl

Every month we try and update this database with for lpl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lpl

Every month we try and update this database with for lpl cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lpl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.