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

Acute Myeloid Leukemia Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03135028
• Other study ID #: GS-US-429-4104
• Status: Terminated
• Phase: Phase 1
• Start date: May 19, 2017
• Est. completion date: February 26, 2019

Study information

• Verified date: February 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: February 26, 2019
• Est. primary completion date: February 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Hematologic Malignancy
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasms

Intervention

Drug:
• Entospletinib
400 mg (2 × 200 mg tablets) orally twice daily
• Daunorubicin
60 mg/m^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle
• 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

Locations

Country	Name	City	State
Japan	University of Fukui Hospital	Fukui
Japan	Kyushu University Hospital	Fukuoka
Japan	Tokai University Hospital	Kanagawa
Japan	Tohoku University Hospital	Miyagi
Japan	Kindai University Hospital	Osaka
Japan	NTT Medical Center Tokyo	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Cycle 1 (28-day cycle)
Secondary	Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT		Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks)
Secondary	Plasma Concentration of ENTO	Plasma concentration of drug (ENTO) over different time points is reported.	Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose