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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Mantle Cell Lymphoma; Diffuse Large B-cell Lymphoma; Chronic Lymphocytic Leukemia; Indolent Non-Hodgkin's Lymphoma

Treatments: Drug: Entospletinib; Drug: Idelalisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01796470

GS-US-339-0103

Details and patient eligibility

About

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]).

Enrollment: 66 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Diagnosis of B-cell indolent non-Hodgkin lymphoma (iNHL),diffuse large B-cell lymphoma (DLBCL),mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (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®; GS-1101); individuals with malignancies being studied in these protocols must have failed screening and be registered as a screen failure in the respective idelalisib protocol
• Prior treatment for lymphoid malignancy
• Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy
• Discontinuation of all therapy for the treatment of cancer ≥ 3 weeks before the start of study drug
• 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 NHL (ie, Richter transformation)
• Known active central nervous system or leptomeningeal lymphoma
• Presence of known intermediate- or high-grade myelodysplastic syndrome
• Current therapy with agents that reduce gastric acidity, including but not limited to antacids, H2 inhibitors, and proton pump inhibitors
• 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.

Trial design

66 participants in 1 patient group

Entospletinib + idelalisib

Experimental group

Description:

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.

Treatment:

Drug: Idelalisib

Drug: Entospletinib