Clinical trial NCT01796470: Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Diffuse Large B-cell Lymphoma
Indolent Non-Hodgkin's Lymphoma
Keywords: GS-US-339-0103
SYK inhibitor
PI3K inhibitor
GS-9973
GS 9973
GS-1101
GS 1101
Cal-101
Cal 101
idelalisib
leukemia
lymphoma
CLL
MCL
DLBCL
iNHL
FL
MZL
LPL
SLL
WM
Waldenström's macroglobulinemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-02-21
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 \[MZL\]).


Eligibility 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Start of treatment to end of treatment (Up to 18 months)
Secondary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to the last dose date plus 30 days (maximum duration: 19 months)
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to the last dose date plus 30 days (maximum: 18 months)
measure: Maximum Tolerated Dose Level
timeFrame: First dose (entospelinib + idelalisib) date up to 6 months
measure: Progression-free Survival (PFS)
timeFrame: Start of treatment to end of treatment (Up to 18 months)
measure: Duration of Response (DOR)
timeFrame: Start of treatment to end of treatment (Up to 18 months)
measure: Time to Response (TTR)
timeFrame: Start of treatment to end of treatment (Up to 18 months)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology Oncology Specialists
state: California
city: Santa Barbara
country: United States
facility: Cancer Center of Santa Barbara
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Boynton Beach
country: United States
facility: Collaborative Research Group LLC
state: Florida
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester, James P. Wilmot Cancer Center
state: New York
city: Middletown
country: United States
facility: Signal Point Clinical Research Center, LLC
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: Charleston Hematology Oncology
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Barr PM, Saylors GB, Spurgeon SE, Cheson BD, Greenwald DR, O'Brien SM, Liem AK, Mclntyre RE, Joshi A, Abella-Dominicis E, Hawkins MJ, Reddy A, Di Paolo J, Lee H, He J, Hu J, Dreiling LK, Friedberg JW. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL. Blood. 2016 May 19;127(20):2411-5. doi: 10.1182/blood-2015-12-683516. Epub 2016 Mar 11.