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

Phase 1TerminatedNCT03135028

Gilead Sciences9 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hematologic Malignancy Acute Myeloid Leukemia

Interventions

EntospletinibDRUG

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

DaunorubicinDRUG

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

CytarabineDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (6)

University of Fukui Hospital

Fukui, Japan

Kyushu University Hospital

Fukuoka, Japan

Tokai University Hospital

Kanagawa, Japan

Tohoku University Hospital

Miyagi, Japan

Outcomes

Primary Outcomes

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.

Time frame: Cycle 1 (28-day cycle)

Secondary Outcomes

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)

Plasma Concentration of ENTO

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.