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

NCT ID: NCT03135028

Last Updated: 2020-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-19
• Study Completion Date: 2019-02-26

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.

Conditions

Hematologic Malignancy; Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ENTO monotherapy (Group A)

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.

Group Type: EXPERIMENTAL

Entospletinib

Intervention Type: DRUG

400 mg (2 × 200 mg tablets) orally twice daily

ENTO + cytarabine + daunorubicin (Group B)

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.

Group Type: EXPERIMENTAL

Entospletinib

Intervention Type: DRUG

400 mg (2 × 200 mg tablets) orally twice daily

Daunorubicin

Intervention Type: DRUG

60 mg/m\^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle

Cytarabine

Intervention Type: DRUG

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

Interventions

Entospletinib

400 mg (2 × 200 mg tablets) orally twice daily

Intervention Type: DRUG

Daunorubicin

60 mg/m\^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle

Intervention Type: DRUG

Cytarabine

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

Intervention Type: DRUG

Other Intervention Names

GS-9973; ENTO

Eligibility Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

University of Fukui Hospital

Fukui, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Tokai University Hospital

Kanagawa, , Japan

Tohoku University Hospital

Miyagi, , Japan

Kindai University Hospital

Ōsaka, , Japan

NTT Medical Center Tokyo

Tokyo, , Japan

Countries

Japan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-429-4104

Identifier Type: -

Identifier Source: org_study_id