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

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ClinicalTrials.gov Identifier: NCT02343939
Recruitment Status : Terminated
First Posted : January 22, 2015
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
This study will evaluate the efficacy, safety, and tolerability of entospletinib (GS-9973) when administered as monotherapy or in combination with chemotherapy in adults with acute myeloid leukemia (AML).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Entospletinib Drug: Daunorubicin Drug: Cytarabine Drug: Decitabine Drug: Azacitidine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 148 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination With Chemotherapy in Patients With Acute Myeloid Leukemia (AML)
Actual Study Start Date : July 1, 2015
Actual Primary Completion Date : October 3, 2018
Actual Study Completion Date : February 21, 2019


Arm Intervention/treatment
Experimental: 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.

Drug: Entospletinib
Tablet(s) administered orally every 12 hours
Other Name: GS-9973

Drug: Daunorubicin
60 mg/m^2 administered intravenously daily on Days 1 to 3 of each 14-day induction cycle

Drug: Cytarabine
100 mg/m^2 administered intravenously daily on Days 1 to 7 of each 14-day cycle

Experimental: 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.

Drug: Entospletinib
Tablet(s) administered orally every 12 hours
Other Name: GS-9973

Drug: Decitabine
20 mg/m^2 administered intravenously

Drug: Azacitidine
75 mg/m^2 administered intravenously or subcutaneously

Experimental: 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.

Drug: Entospletinib
Tablet(s) administered orally every 12 hours
Other Name: GS-9973




Primary Outcome Measures :
  1. Occurrence of adverse events (AEs) and laboratory abnormalities defined as dose limiting toxicities (DLTs) for each treatment group [ Time Frame: Up to 2 years ]
    This composite endpoint will measure the safety and tolerability profile of entospletinib.

  2. Complete remission rate at induction completion [ Time Frame: Up to 2 years ]
    Complete remission rate at induction completion is defined as the proportion of participants who achieved morphologic complete remission (CR) at induction completion.

  3. Composite complete remission rate at induction completion [ Time Frame: Up to 2 years ]
    Composite complete remission rate at induction completion is defined as the proportion of subjects who achieved CR or morphologic complete remission with incomplete blood count recovery (CRi) at induction completion

  4. Overall response rate at induction completion [ Time Frame: Up to 2 years ]
    Overall response rate at induction completion is defined as the proportion of subjects who achieved CR, CRi, or partial remission (PR) at induction completion.


Secondary Outcome Measures :
  1. Study drug administration [ Time Frame: Up to 2 years ]
    Study drug administration will be measured by the number of doses of study therapy prescribed and the total number of doses taken.

  2. Duration of exposure of study treatment [ Time Frame: Up to 2 years ]
    The duration of exposure will be summarized for each group.

  3. Occurrence of AEs and laboratory abnormalities not defined as DLTs [ Time Frame: Up to 2 years ]
  4. Event free survival (EFS) [ Time Frame: Up to 2 Years ]
    EFS is defined for all participants and is measured from the start of the study therapy until the date of treatment failure, AML relapse, or death from any cause, whichever occurs first.

  5. Overall survival (OS) [ Time Frame: Up to 2 Years ]
    OS is defined as the interval from the start of the study therapy to death from any cause.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Adults with AML in need of treatment
  • Group A : Individuals > 18 years of age with previously untreated AML 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 or individuals < 70 years of age with previously untreated AML who refuse or are unable to receive cytarabine as determined by the treating physician
  • Group C: Cohort C1A: Subjects age ≥ 18 years with relapsed/refractory AML by WHO criteria; Cohort C2: Subjects age ≥ 18 years with relapsed/refractory AML with MLL; Cohort C3: Subjects 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02343939


Locations
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United States, California
UCLA
Los Angeles, California, United States
United States, Illinois
University of Chicago
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
United States, Indiana
Indiana University
Indianapolis, Indiana, United States
United States, Kansas
University of Kansas Medical Center Research Institute, Inc
Fairway, Kansas, United States
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
United States, New York
Weill Cornell Medical College - New York - Presbyterian Hospital
New York, New York, United States
United States, North Carolina
Duke Cancer Center
Durham, North Carolina, United States
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, South Carolina
Saint Francis Cancer Center
Greenville, South Carolina, United States
Canada, Ontario
Princess Margaret
Toronto, Ontario, Canada
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada
Germany
Universitätsklinikum Frankfurt Medizinische Klinik II
Frankfurt, Germany, 60590
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02343939     History of Changes
Other Study ID Numbers: GS-US-339-1559
First Posted: January 22, 2015    Key Record Dates
Last Update Posted: March 12, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Azacitidine
Decitabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors