Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Idelalisib

Enzyme Inhibitors

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

Gilead Study Director

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.

Gilead Sciences

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.

Total

Age, Continuous

Sex: Female, Male

Ethnicity

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

Race/Ethnicity, Customized

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)

Anemia (Grade 4)

Leukocytosis (Grade 1)

Leukocytosis (Grade 2)

Leukocytosis (Grade 3)

Leukocytosis (Grade 4)

White Blood Cell Count Decreased (Grade 1)

WBC Count Decreased (Grade 2)

WBC Count Decreased (Grade 3)

WBC Count Decreased (Grade 4)

Lymphocyte Count Decreased (Grade 1)

Lymphocyte Count Decreased (Grade 2)

Lymphocyte Count Decreased (Grade 3)

Lymphocyte Count Decreased (Grade 4)

Lymphocyte Count Increased (Grade 1)

Lymphocyte Count Increased (Grade 2)

Lymphocyte Count Increased (Grade 3)

Lymphocyte Count Increased (Grade 4)

Platelets Count Decreased (Grade 1)

Platelets Count Decreased (Grade 2)

Platelets Count Decreased (Grade 3)

Platelets Count Decreased (Grade 4)

Alanine Aminotransferase (ALT) Increased (Grade 1)

ALT Increased (Grade 2)

ALT Increased (Grade 3)

ALT Increased (Grade 4)

Hypoalbuminemia (Grade 1)

Hypoalbuminemia (Grade 2)

Hypoalbuminemia (Grade 3)

Hypoalbuminemia (Grade 4)

Alkaline Phosphatase (ALP) Increased (Grade 1)

ALP Increased (Grade 2)

ALP Increased (Grade 3)

ALP Increased (Grade 4)

Aspartate Aminotransferase (AST)Increased(Grade 1)

AST Increased (Grade 2)

AST Increased (Grade 3)

AST Increased (Grade 4)

Chronic Kidney Disease (Grade 1)

Chronic Kidney Disease (Grade 2)

Chronic Kidney Disease (Grade 3)

Chronic Kidney Disease (Grade 4)

Hyperglycemia (Grade 1)

Hyperglycemia (Grade 2)

Hyperglycemia (Grade 3)

Hyperglycemia (Grade 4)

Hypoglycemia (Grade 1)

Hypoglycemia (Grade 2)

Hypoglycemia (Grade 3)

Hypoglycemia (Grade 4)

Hypophosphatemia (Grade 1)

Hypophosphatemia (Grade 2)

Hypophosphatemia (Grade 3)

Hypophosphatemia (Grade 4)

Hypokalemia (Grade 1)

Hypokalemia (Grade 2)

Hypokalemia (Grade 3)

Hypokalemia (Grade 4)

Hyponatremia (Grade 1)

Hyponatremia (Grade 2)

Hyponatremia (Grade 3)

Hyponatremia (Grade 4)

Blood Bilirubin Increased (Grade 1)

Blood Bilirubin Increased (Grade 2)

Blood Bilirubin Increased (Grade 3)

Blood Bilirubin Increased (Grade 4)

Proteinuria (Grade 1)

Proteinuria (Grade 2)

Proteinuria (Grade 3)

Proteinuria (Grade 4)

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.

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.

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.

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.

Participants in the Safety Analysis Set were analyzed.

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

Spots Global Cancer Trial Database for Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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