Acute Myeloid LeukemiaPhase 1/2ENTO in AMLNCT02343939

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

A Phase 1/2 study testing Entospletinib, Daunorubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Gilead Sciences at 17 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myeloid Leukemia
What is being tested?: Entospletinib, Daunorubicin and Cytarabine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 148 participants
Where: 17 sitesin 3 countries
Study dates: 1 Jul 2015to 21 Feb 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

17 sites in 3 countries.

Country

City, postcode or hospital

17 sites in 3 countries

United States14 sites

Dana Farber Cancer Institute
Boston, Massachusetts
University of Chicago
Chicago, Illinois
University Hospitals Case Medical Center
Cleveland, Ohio
Ohio State University
Columbus, Ohio
Henry Ford Health System
Detroit, Michigan
Karmanos Cancer Institute
Detroit, Michigan
Duke Cancer Center
Durham, North Carolina
University of Kansas Medical Center Research Institute, Inc
Fairway, Kansas
Saint Francis Cancer Center
Greenville, South Carolina
Indiana University
Indianapolis, Indiana
UCLA
Los Angeles, California
Loyola University Medical Center
Maywood, Illinois
Weill Cornell Medical College - New York - Presbyterian Hospital
New York, New York
Oregon Health & Science University
Portland, Oregon, 97239

Other trials in United States

Canada2 sites

Jewish General Hospital
Montreal, Quebec
Princess Margaret
Toronto, Ontario

Other trials in Canada

Germany1 site

Universitätsklinikum Frankfurt Medizinische Klinik II
Frankfurt, 60590

Other trials in Germany

About this study

Official title: A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia (AML)

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).

Conditions: Acute Myeloid Leukemia
Being tested: Entospletinib, Daunorubicin, Cytarabine, Decitabine, Azacitidine
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EntospletinibDrug
Also called GS-9973, ENTO
Tablet(s) administered orally every 12 hours
DaunorubicinDrug
60 mg/m^2 administered intravenously daily on Days 1 to 3 for up to two 14-day induction cycles
CytarabineDrug
100 mg/m^2 administered intravenously daily on Days 1 to 7 for up to two 14-day cycles
DecitabineDrug
20 mg/m^2 administered intravenously
AzacitidineDrug
75 mg/m^2 administered intravenously or subcutaneously

Study groups in NCT02343939
Study group	Role	What they receive
Entospletinib + daunorubicin + cytarabine (Group A)	Experimental	Dose Escalation: Entospletinib up to 400 mg for 14 days and then entospletinib up to 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Dose Expansion: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Some participants will have the option to receive post-induction therapy with entospletinib 400 mg in combination with cytarabine/cytosine arabinoside (ARA-C). Participants may receive maintenance therapy with 28-day cycles of entospletinib 400 mg for up to twelve 28-day cycles, if the participant is not eligible for stem cell transplant. Receives: Drug: Entospletinib; Drug: Daunorubicin; Drug: Cytarabine
Entospletinib + decitabine (Group B)	Experimental	Dose Escalation: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with decitabine for 10 days beginning on Day 1 of every 28-day cycle (at least 2 cycles of induction therapy but no more than 4 cycles). Participants who are intolerant of decitabine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles. Dose Expansion: Entospletinib 400 mg for 14 days for the safety run-in participants or Entospletinib 400 mg for 5 days for the randomization participants. Then entospletinib 400 mg in combination with decitabine or azacitidine (at least 2 cycles of induction therapy but no more than 4 cycles). Some participants will have the option to receive maintenance therapy with entospletinib in combination with decitabine or azacitidine. Participants who are intolerant of decitabine or azacitidine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles. Receives: Drug: Entospletinib; Drug: Decitabine; Drug: Azacitidine
Entospletinib (Group C)	Experimental	Dose Escalation: Entospletinib up to 800 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the study protocol. Dose Expansion: Entospletinib 400 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the protocol. Receives: Drug: Entospletinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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 (5)

Duration of Exposure of Entospletinib
Measured: First dose date up to approximately 3 years
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.
Measured: First dose date up to approximately 38 months
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.
Measured: First dose date up to approximately 38 months
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Measured: First dose date up to the last dose date plus 30 days (maximum: 18 months)
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.
Measured: First dose date up to the last dose date plus 30 days (maximum: 18 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 201521 Feb 2019

First posted22 Jan 2015 (estimated)
Study start1 Jul 2015
Primary completion4 Sep 2018
Study completion21 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 148 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02343939
Sponsor's protocol ID: GS-US-339-1559
Other IDs: 2016-003353-16, 2016
Acronym: ENTO in AML
Status last verified: Nov 2019
First submitted: 16 Jan 2015
Last updated: 15 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia (AML)
ClinicalTrials.gov ID: NCT02343939
Acronym / sponsor ID: ENTO in AML / GS-US-339-1559
Conditions: Acute Myeloid Leukemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 148 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: 1 Jul 2015 (actual)
Primary completion: 4 Sep 2018 (actual)
Study completion: 21 Feb 2019 (actual)
First posted: 22 Jan 2015 (estimated)
Results: Posted 15 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Entospletinib + daunorubicin + cytarabine (Group A)	Experimental	Drug: Entospletinib, Drug: Daunorubicin, Drug: CytarabineDose Escalation: Entospletinib up to 400 mg for 14 days and then entospletinib up to 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Dose Expansion: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Some participants will have the option to receive post-induction therapy with entospletinib 400 mg in combination with cytarabine/cytosine arabinoside (ARA-C). Participants may receive maintenance therapy with 28-day cycles of entospletinib 400 mg for up to twelve 28-day cycles, if the participant is not eligible for stem cell transplant.
Entospletinib + decitabine (Group B)	Experimental	Drug: Entospletinib, Drug: Decitabine, Drug: AzacitidineDose Escalation: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with decitabine for 10 days beginning on Day 1 of every 28-day cycle (at least 2 cycles of induction therapy but no more than 4 cycles). Participants who are intolerant of decitabine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles. Dose Expansion: Entospletinib 400 mg for 14 days for the safety run-in participants or Entospletinib 400 mg for 5 days for the randomization participants. Then entospletinib 400 mg in combination with decitabine or azacitidine (at least 2 cycles of induction therapy but no more than 4 cycles). Some participants will have the option to receive maintenance therapy with entospletinib in combination with decitabine or azacitidine. Participants who are intolerant of decitabine or azacitidine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles.
Entospletinib (Group C)	Experimental	Drug: EntospletinibDose Escalation: Entospletinib up to 800 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the study protocol. Dose Expansion: Entospletinib 400 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the protocol.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EntospletinibAlso: GS-9973, ENTOTablet(s) administered orally every 12 hours	Drug	Entospletinib (Group C), Entospletinib + daunorubicin + cytarabine (Group A), Entospletinib + decitabine (Group B)
Daunorubicin60 mg/m^2 administered intravenously daily on Days 1 to 3 for up to two 14-day induction cycles	Drug	Entospletinib + daunorubicin + cytarabine (Group A)
Cytarabine100 mg/m^2 administered intravenously daily on Days 1 to 7 for up to two 14-day cycles	Drug	Entospletinib + daunorubicin + cytarabine (Group A)
Decitabine20 mg/m^2 administered intravenously	Drug	Entospletinib + decitabine (Group B)
Azacitidine75 mg/m^2 administered intravenously or subcutaneously	Drug	Entospletinib + decitabine (Group B)

Primary outcome

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time frame: 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)
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.
Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction
Time frame: 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)
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.
Percentage of Participants With Composite Complete Remission at the End of Induction
Time frame: 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)
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.
Percentage of Participants With Overall Response at the End of Induction
Time frame: 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)
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.

5 secondary outcomes

Duration of Exposure of Entospletinib
Time frame: First dose date up to approximately 3 years
Event Free Survival (EFS)
Time frame: First dose date up to approximately 38 months
Overall Survival (OS)
Time frame: First dose date up to approximately 38 months
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: First dose date up to the last dose date plus 30 days (maximum: 18 months)
Percentage of Participants Who Experienced Laboratory Abnormalities
Time frame: First dose date up to the last dose date plus 30 days (maximum: 18 months)

Results and safety

Results posted to the registry on 15 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	3	0
Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	50	2
Group B Phase 1b ENTO 200 mg + Decitabine	5	0
Group B Phase 1b ENTO 400 mg + Decitabine	6	0
Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	8	0
Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	17	0
Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	15	0
Group C Phase 1b/2 ENTO 400 mg	37	0
Group C Phase 1b ENTO 800 mg	7	0

Primary outcome: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

Time frame: 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). Number. Unit: percentage of participants

Measure	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin n = 3	Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin n = 6	Group B Phase 1b ENTO 200 mg + Decitabine n = 3	Group B Phase 1b ENTO 400 mg + Decitabine n = 6	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) n = 6	Group C Phase 1b/2 ENTO 400 mg n = 6	Group C Phase 1b ENTO 800 mg n = 6
Value	0	0	0	16.7	0	0	16.7

Population analysed: The DLT Analysis Set included all participants who received 21 days of ENTO (applicable to all groups) and all doses of cytarabine and daunorubicin in Group A Phase 1b, decitabine in Group B Phase 1b, or azacitidine in Group B Phase 2 safety run-in during the DLT assessment window; or experienced a DLT during the DLT assessment window.

Primary outcome: Percentage of Participants With Morphologic Complete Remission (CR) at the End of Induction

Time frame: 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). Number (95% Confidence Interval). Unit: percentage of participants

Measure	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin n = 3	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin n = 9	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin n = 41	Group B Phase 1b ENTO 200 mg + Decitabine n = 5	Group B Phase 1b ENTO 400 mg + Decitabine n = 6	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) n = 8	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) n = 17	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) n = 14	Group C Phase 1b ENTO 400 mg n = 7	Group C Phase 1b ENTO 800 mg n = 7	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) n = 6	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) n = 13	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) n = 9
Value	66.7 (9.4 to 99.2)	66.7 (29.9 to 92.5)	46.3 (30.7 to 62.6)	0.0 (0.0 to 52.2)	16.7 (0.4 to 64.1)	25.0 (3.2 to 65.1)	0.0 (0.0 to 19.5)	7.1 (0.2 to 33.9)	0.0 (0.0 to 41.0)	0.0 (0.0 to 41.0)	0.0 (0.0 to 45.9)	15.4 (1.9 to 45.4)	11.1 (0.3 to 48.2)

Population analysed: The Full Analysis Set included all participants who received at least 1 dose of study drug with treatment designated according to the planned treatment.

Primary outcome: Percentage of Participants With Composite Complete Remission at the End of Induction

Measure	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin n = 3	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin n = 9	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin n = 41	Group B Phase 1b ENTO 200 mg + Decitabine n = 5	Group B Phase 1b ENTO 400 mg + Decitabine n = 6	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) n = 8	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) n = 17	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) n = 14	Group C Phase 1b ENTO 400 mg n = 7	Group C Phase 1b ENTO 800 mg n = 7	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) n = 6	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) n = 13	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) n = 9
Value	100.0 (29.2 to 100)	77.8 (40 to 97.2)	65.9 (49.4 to 79.9)	40.0 (5.3 to 85.3)	50.0 (11.8 to 88.2)	25.0 (3.2 to 65.1)	23.5 (6.8 to 49.9)	14.3 (1.8 to 42.8)	14.3 (0.4 to 57.9)	0.0 (0.0 to 41.0)	0.0 (0.0 to 45.9)	15.4 (1.9 to 45.4)	11.1 (0.3 to 48.2)

Population analysed: Participants in the Full Analysis Set were analyzed.

Primary outcome: Percentage of Participants With Overall Response at the End of Induction

Measure	Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin n = 3	Group A Phase 1b ENTO 400 mg + Cytarabine + Daunorubicin n = 9	Group A Phase 2 ENTO 400 mg + Cytarabine + Daunorubicin n = 41	Group B Phase 1b ENTO 200 mg + Decitabine n = 5	Group B Phase 1b ENTO 400 mg + Decitabine n = 6	Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In) n = 8	Group B Phase 2 ENTO 400 mg + Decitabine (Randomized) n = 17	Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized) n = 14	Group C Phase 1b ENTO 400 mg n = 7	Group C Phase 1b ENTO 800 mg n = 7	Group C Phase 2 ENTO 400 mg (Cohort C1A - R/R AML) n = 6	Group C Phase 2 ENTO 400 mg (Cohort C2 - MLL) n = 13	Group C Phase 2 ENTO 400 mg (Cohort C3 - Untreated AML) n = 9
Value	100.0 (29.2 to 100)	77.8 (40 to 97.2)	70.7 (54.5 to 83.9)	40.0 (5.3 to 85.3)	50.0 (11.8 to 88.2)	25.0 (3.2 to 65.1)	23.5 (6.8 to 49.9)	14.3 (1.8 to 42.8)	14.3 (0.4 to 57.9)	0.0 (0 to 41)	0.0 (0 to 45.9)	15.4 (1.9 to 45.4)	11.1 (0.3 to 48.2)

Population analysed: Participants in the Full Analysis Set were analyzed.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: - All-Cause Mortality: First dose date up to approximately 38 months. - Adverse Events: First dose date up to the last dose date plus 30 days (maximum: 18 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A Phase 1b ENTO 200 mg + Cytarabine + Daunorubicin	0 of 3 (0%)	3 of 3 (100%)	2 of 3
Group A Phase 1b/2 ENTO 400 mg + Cytarabine + Daunorubicin	23 of 50 (46%)	50 of 50 (100%)	21 of 50
Group B Phase 1b ENTO 200 mg + Decitabine	5 of 5 (100%)	5 of 5 (100%)	5 of 5
Group B Phase 1b ENTO 400 mg + Decitabine	5 of 6 (83.3%)	6 of 6 (100%)	4 of 6
Group B Phase 2 ENTO 400 mg + Azacitidine (Safety Run-In)	7 of 8 (87.5%)	7 of 8 (87.5%)	5 of 8
Group B Phase 2 ENTO 400 mg + Decitabine (Randomized)	11 of 17 (64.7%)	17 of 17 (100%)	12 of 17
Group B Phase 2 ENTO 400 mg + Azacitidine (Randomized)	7 of 14 (50%)	14 of 14 (100%)	11 of 14
Group C Phase 1b/2 ENTO 400 mg	19 of 35 (54.3%)	33 of 35 (94.3%)	30 of 35
Group C Phase 1b ENTO 800 mg	4 of 7 (57.1%)	7 of 7 (100%)	6 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gilead Study Director study director

Gilead Sciences

17 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Entospletinib, Daunorubicin and Cytarabine in people with Acute Myeloid Leukemia, run by Gilead Sciences at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) (time frame: 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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02343939.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2019.