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Entospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults (Japanese AML)

Primary Purpose

Hematologic Malignancy, Acute Myeloid Leukemia

Status
Terminated
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Entospletinib
Daunorubicin
Cytarabine
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancy focused on measuring Relapsed or Refractory Hematologic Malignancy, Previously untreated AML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • ENTO monotherapy (Group A): relapsed or refractory hematologic malignancies by World Health Organisation (WHO) criteria and who are not eligible to receive standard of care
  • ENTO + cytarabine + daunorubicin (Group B): previously untreated AML by WHO criteria, who are deemed fit for cytarabine and daunorubicin (7+3) induction chemotherapy and are able to undergo up to 2 cycles of induction chemotherapy, as determined by the treating physician
  • Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1 of study treatment
  • Must be able to confirm the Japanese origin of their maternal and paternal ancestry

Key Exclusion Criteria:

  • Known active central nervous system or leptomeningeal leukemic involvement
  • Ongoing liver injury, or known infection with chronic active hepatitis C virus (HCV) or chronic active hepatitis B virus (HBV)

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

Sites / Locations

  • University of Fukui Hospital
  • Kyushu University Hospital
  • Tokai University Hospital
  • Tohoku University Hospital
  • NTT Medical Center Tokyo
  • Kindai University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ENTO monotherapy (Group A)

ENTO + cytarabine + daunorubicin (Group B)

Arm Description

Participants with relapsed or refractory hematologic malignancies will receive ENTO twice daily of every 28-day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit.

Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days. Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles. Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT: Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue. In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours Liver function test abnormalities that did not resolve to Grade 2 within 10 days Infection that resulted from unexpectedly complicated prolonged myelosuppression Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.

Secondary Outcome Measures

Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT
Plasma Concentration of ENTO
Plasma concentration of drug (ENTO) over different time points is reported.

Full Information

First Posted
April 26, 2017
Last Updated
February 21, 2020
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT03135028
Brief Title
Entospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults
Acronym
Japanese AML
Official Title
A Phase 1b Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Entospletinib (ENTO) as Monotherapy in Japanese Subjects With Relapsed or Refractory Hematologic Malignancies and in Combination With Chemotherapy in Japanese Subjects With Previously Untreated Acute Myeloid Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
No signal of efficacy with Entospletinib
Study Start Date
May 19, 2017 (Actual)
Primary Completion Date
February 26, 2019 (Actual)
Study Completion Date
February 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of this study is to evaluate the safety and tolerability of entospletinib (ENTO) monotherapy and in combination with chemotherapy in Japanese participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancy, Acute Myeloid Leukemia
Keywords
Relapsed or Refractory Hematologic Malignancy, Previously untreated AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ENTO monotherapy (Group A)
Arm Type
Experimental
Arm Description
Participants with relapsed or refractory hematologic malignancies will receive ENTO twice daily of every 28-day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit.
Arm Title
ENTO + cytarabine + daunorubicin (Group B)
Arm Type
Experimental
Arm Description
Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days. Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles. Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles.
Intervention Type
Drug
Intervention Name(s)
Entospletinib
Other Intervention Name(s)
GS-9973, ENTO
Intervention Description
400 mg (2 × 200 mg tablets) orally twice daily
Intervention Type
Drug
Intervention Name(s)
Daunorubicin
Intervention Description
60 mg/m^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
100 mg/m^2 intravenous administration twice daily on Days 1 to 7 of each 28-day induction cycle Hi-DAC: 3 g/m^2 IV administration twice daily on days 1, 3, and 5 (≤ 60 years of age) or 1 g/m^2 IV administration once daily on Days 1 to 5 (> 60 years of age) of each 28-day post-remission cycle
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
Description
Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT: Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue. In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours Liver function test abnormalities that did not resolve to Grade 2 within 10 days Infection that resulted from unexpectedly complicated prolonged myelosuppression Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.
Time Frame
Cycle 1 (28-day cycle)
Secondary Outcome Measure Information:
Title
Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT
Time Frame
Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks)
Title
Plasma Concentration of ENTO
Description
Plasma concentration of drug (ENTO) over different time points is reported.
Time Frame
Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: ENTO monotherapy (Group A): relapsed or refractory hematologic malignancies by World Health Organisation (WHO) criteria and who are not eligible to receive standard of care ENTO + cytarabine + daunorubicin (Group B): previously untreated AML by WHO criteria, who are deemed fit for cytarabine and daunorubicin (7+3) induction chemotherapy and are able to undergo up to 2 cycles of induction chemotherapy, as determined by the treating physician Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1 of study treatment Must be able to confirm the Japanese origin of their maternal and paternal ancestry Key Exclusion Criteria: Known active central nervous system or leptomeningeal leukemic involvement Ongoing liver injury, or known infection with chronic active hepatitis C virus (HCV) or chronic active hepatitis B virus (HBV) NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
University of Fukui Hospital
City
Fukui
ZIP/Postal Code
910-1193
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Tokai University Hospital
City
Kanagawa
ZIP/Postal Code
259-1193
Country
Japan
Facility Name
Tohoku University Hospital
City
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
NTT Medical Center Tokyo
City
Tokyo
ZIP/Postal Code
141-8625
Country
Japan
Facility Name
Kindai University Hospital
City
Ōsaka
ZIP/Postal Code
589-8511
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
No

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Entospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults

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