NCT01799889 - Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key 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 Key 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 NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Week 24

Secondary Outcomes

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.

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

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

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

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

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)

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.

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)

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.

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)

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.

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)

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

Overview

Conditions

Interventions

Eligibility

Locations (48)

Outcomes

Primary Outcomes

Secondary Outcomes