Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Neoplasms

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Daunorubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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.

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

Entospletinib

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

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

Gilead Study Director

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.

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

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)

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.

Plasma concentration of drug (ENTO) over different time points is reported.

Gilead Sciences

Full Analysis Set included all participants who received at least 1 dose of study drug (ENTO).

Participants received ENTO 400 mg (2 × 200 mg tablets) orally twice daily in a fasted state on Days 1 through 28 of every 28-day cycle, and continued on study treatment as long as the participant experienced benefit and did not meet the criteria for study treatment discontinuation.

ENTO 400 mg

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

Ethnicity

The study was terminated early due to sponsor's decision based on the results from the Phase 1b/2 Study GS-US-339-1559 (NCT02343939) in participants with Acute Myeloid Leukemia and reorganization of the drug development portfolio.

Gilead Clinical Study Information Center

The DLT Analysis Set included all participants in the Full Analysis Set (all participants who received at least 1 dose of study drug \[ENTO\]) who received at least 21 days of ENTO or experienced a DLT during DLT assessment window.

Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)

Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT

Cycle 1 Day 8, predose

Cycle 1 Day 8, 1 hour postdose

Cycle 1 Day 8, 2 hours postdose

Cycle 1 Day 8, 3 hours postdose

Cycle 1 Day 8, 4 hours postdose

Cycle 1 Day 8, 6 hours postdose

Cycle 1 Day 8, 8 hours postdose

Cycle 1 Day 8, 12 hours postdose

Pharmacokinetic (PK) Analysis Set included all participants in the Full Analysis Set who had necessary baseline and at least 1 non-missing post-treatment assessments. Participants with available data were analyzed. PK parameters were not derived from the collected data due to the early study termination.

Plasma Concentration of ENTO

Participants received entospletinib (ENTO) 400 mg (2 × 200 mg tablets) orally twice daily in a fasted state on Days 1 through 28 of every 28-day cycle, and continued on study treatment as long as the participant experienced benefit and did not meet the criteria for study treatment discontinuation.

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