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

Gilead Sciences

Status and phase: Terminated; Phase 2

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

Treatments: Drug: Entospletinib SDD; Drug: Entospletinib MM

Study type: Interventional

Funder types: Industry

Identifiers

NCT01799889

GS-US-339-0102

Details and patient eligibility

About

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]).

Enrollment: 326 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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326 participants in 12 patient groups

CLL, Entospletinib MM/SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib MM

Drug: Entospletinib SDD

FL, Entospletinib MM/SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib MM

Drug: Entospletinib SDD

DLBCL, Entospletinib MM/SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib MM

Drug: Entospletinib SDD

MCL, Entospletinib MM/SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib MM

Drug: Entospletinib SDD

non-FL iNHL, Entospletinib MM/SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib MM

Drug: Entospletinib SDD

CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD

CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 200 mg

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD

CLL; Prior BCR Inhibitor Naive, Entospletinib SDD 400 mg

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD

CLL (Non-Richters) Prior BTK Inhibitor, Entospletinib SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD

CLL (Non-Richters) Prior PI3K Inhibitor, Entospletinib SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD

CLL (Richters) Prior BTK Inhibitor, Entospletinib SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD

CLL (Richters) Prior PI3K Inhibitor, Entospletinib SDD

Experimental group

Description:

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.

Treatment:

Drug: Entospletinib SDD