Clinical trial NCT02343939: Entospletinib Monotherapy and in Combination With Chemotherapy in Adults With Acute Myeloid Leukemia (AML)
Official title: A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-01-22
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, and tolerability of entospletinib when administered as monotherapy or in combination with chemotherapy in adults with acute myeloid leukemia (AML).


Eligibility criteria: Key Inclusion Criteria:

* Adults with AML in need of treatment
* Group A : Individuals ≥ 18 years of age with previously untreated AML by World Health Organization (WHO) criteria who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician
* Group B: Individuals \> 70 years of age with previously untreated AML by WHO criteria; or individuals ≤ 70 years of age with previously untreated AML who refuse or are unable to receive chemotherapy with 7+3 as determined by the treating physician
* Group C: Individuals ≥ 18 years of age with relapsed/refractory AML by WHO criteria; or with relapsed/refractory AML with mixed-lineage leukemia (MLL); or with previously untreated AML by WHO criteria and who would have met disease eligibility criteria for Group A or B but refuse or are unable to receive chemotherapy and hypomethylating agent as determined by the treating physician

Key Exclusion Criteria:

* Known active central nervous system or leptomeningeal lymphoma
* Subjects with acute promyelocytic leukemia (M3)
* Treatment with proton pump inhibitors (PPIs) within 7 days prior to enrollment.

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

Primary outcomes:
measure: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: Group A: Cycle 0 Day 1 to Cycle 2 Day 28; Group B: Cycle 0 Day 1 to Cycle 1 Day 28; Group C: Cycle 1 Day 1 to Cycle 1 Day 28 (Cycle length: for Cycle 0 = 14 days, for all other cycles = 28 days)
measure: Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction
timeFrame: At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)
measure: Percentage of Participants With Composite Complete Remission at the End of Induction
timeFrame: At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)
measure: Percentage of Participants With Overall Response at the End of Induction
timeFrame: At the end of induction (Group A: up to end of Cycle 2; Group B: up to end of Cycle 4) (cycle length = up to 28 days); Group C: From Day 1 until meeting the criteria for study treatment discontinuation (up to approximately 3 years)
Secondary outcomes:
measure: Duration of Exposure of Entospletinib
timeFrame: First dose date up to approximately 3 years
measure: Event Free Survival (EFS)
timeFrame: First dose date up to approximately 38 months
measure: Overall Survival (OS)
timeFrame: First dose date up to approximately 38 months
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First dose date up to the last dose date plus 30 days (maximum: 18 months)
measure: Percentage of Participants Who Experienced Laboratory Abnormalities
timeFrame: First dose date up to the last dose date plus 30 days (maximum: 18 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Medical Center Research Institute, Inc
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical College - New York - Presbyterian Hospital
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Toronto
country: Canada
facility: Princess Margaret
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Medizinische Klinik II
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: