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

NCT ID: NCT02343939

Last Updated: 2019-11-15

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-01

Study Completion Date

2019-02-21

Brief Summary

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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).

Detailed Description

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Conditions

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Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Entospletinib + daunorubicin + cytarabine (Group A)

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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Tablet(s) administered orally every 12 hours

Daunorubicin

Intervention Type DRUG

60 mg/m\^2 administered intravenously daily on Days 1 to 3 for up to two 14-day induction cycles

Cytarabine

Intervention Type DRUG

100 mg/m\^2 administered intravenously daily on Days 1 to 7 for up to two 14-day cycles

Entospletinib + decitabine (Group B)

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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Tablet(s) administered orally every 12 hours

Decitabine

Intervention Type DRUG

20 mg/m\^2 administered intravenously

Azacitidine

Intervention Type DRUG

75 mg/m\^2 administered intravenously or subcutaneously

Entospletinib (Group C)

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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Tablet(s) administered orally every 12 hours

Interventions

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Entospletinib

Tablet(s) administered orally every 12 hours

Intervention Type DRUG

Daunorubicin

60 mg/m\^2 administered intravenously daily on Days 1 to 3 for up to two 14-day induction cycles

Intervention Type DRUG

Cytarabine

100 mg/m\^2 administered intravenously daily on Days 1 to 7 for up to two 14-day cycles

Intervention Type DRUG

Decitabine

20 mg/m\^2 administered intravenously

Intervention Type DRUG

Azacitidine

75 mg/m\^2 administered intravenously or subcutaneously

Intervention Type DRUG

Other Intervention Names

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GS-9973 ENTO

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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UCLA

Los Angeles, California, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Kansas Medical Center Research Institute, Inc

Fairway, Kansas, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Weill Cornell Medical College - New York - Presbyterian Hospital

New York, New York, United States

Site Status

Duke Cancer Center

Durham, North Carolina, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Saint Francis Cancer Center

Greenville, South Carolina, United States

Site Status

Princess Margaret

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Universitätsklinikum Frankfurt Medizinische Klinik II

Frankfurt, , Germany

Site Status

Countries

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United States Canada Germany

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-003353-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-339-1559

Identifier Type: -

Identifier Source: org_study_id

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