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

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Hematologic Malignancy; Acute Myeloid Leukemia

Treatments: Drug: Daunorubicin; Drug: Entospletinib; Drug: Cytarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03135028

GS-US-429-4104

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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9 participants in 2 patient groups

ENTO monotherapy (Group A)

Experimental group

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.

Treatment:

Drug: Entospletinib

ENTO + cytarabine + daunorubicin (Group B)

Experimental group

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.

Treatment:

Drug: Entospletinib

Drug: Daunorubicin

Drug: Cytarabine