Entospletinib Monotherapy and in Combination With Chemotherapy in Adults With Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia Clinical Trial

— ENTO in 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02343939
• Other study ID #: GS-US-339-1559
• Secondary ID: 2016-003353-16
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 1, 2015
• Est. completion date: February 21, 2019

Study information

• Verified date: November 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 148
• Est. completion date: February 21, 2019
• Est. primary completion date: September 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Entospletinib
Tablet(s) administered orally every 12 hours
• Daunorubicin
60 mg/m^2 administered intravenously daily on Days 1 to 3 for up to two 14-day induction cycles
• Cytarabine
100 mg/m^2 administered intravenously daily on Days 1 to 7 for up to two 14-day cycles
• Decitabine
20 mg/m^2 administered intravenously
• Azacitidine
75 mg/m^2 administered intravenously or subcutaneously

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Princess Margaret	Toronto	Ontario
Germany	Universitätsklinikum Frankfurt Medizinische Klinik II	Frankfurt
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke Cancer Center	Durham	North Carolina
United States	University of Kansas Medical Center Research Institute, Inc	Fairway	Kansas
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Indiana University	Indianapolis	Indiana
United States	UCLA	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Weill Cornell Medical College - New York - Presbyterian Hospital	New York	New York
United States	Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)	DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment. DLT assessment was applicable only for Phase 1b and Phase 2 safety run-in participants.	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)
Primary	Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction	Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Morphologic CR included CR and cytogenetic CR (CRc). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils = 1,000/microliter (mcL); Platelets = 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis.	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)
Primary	Percentage of Participants With Composite Complete Remission at the End of Induction	Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Composite complete remission included CR, CRc, and morphologic complete remission with incomplete blood count recovery (CRi). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils = 1,000/mcL; Platelets = 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets.	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)
Primary	Percentage of Participants With Overall Response at the End of Induction	Clinical response was assessed according to the International Working Group criteria (Cheson 2003). Overall response included CR, CRc, CRi, and partial remission (PR). CR required all of the following: < 5% blasts in bone marrow aspirate; Neutrophils = 1,000/mcL; Platelets = 100,000/mcL; No extramedullary disease; No blasts with Auer rods detected; and Independent of transfusions. CRc, in addition to CR criteria, required reversion to a normal karyotype with an abnormal karyotype at the time of diagnosis. CRi required all of the CR criteria except the criterion of neutrophils and platelets. PR required all of the following: = 50% decrease in blasts in bone marrow aspirate to a range of 5% to 25%; Neutrophils = 1,000/mcL; Platelets = 100,000/mcL; Independent of transfusions; and A value of = 5% blasts was also considered a PR if Auer rods were detected.	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	Duration of Exposure of Entospletinib		First dose date up to approximately 3 years
Secondary	Event Free Survival (EFS)	EFS was defined as the time interval from the start of the study therapy until the date of treatment failure, acute myeloid leukemia (AML) relapse, or death from any cause, whichever occurred first. Participants who received other anti-cancer therapy (prior to the event if any) were censored. Median EFS was analyzed using Kaplan-Meier (KM) method.	First dose date up to approximately 38 months
Secondary	Overall Survival (OS)	OS was defined as the time interval from the start of the study therapy to death from any cause. Median OS was analyzed using KM method.	First dose date up to approximately 38 months
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events		First dose date up to the last dose date plus 30 days (maximum: 18 months)
Secondary	Percentage of Participants Who Experienced Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.	First dose date up to the last dose date plus 30 days (maximum: 18 months)