Trial Outcomes & Findings for Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) (NCT NCT02404220)

Last Updated: 2020-01-02

Results Overview

The occurrence of any of the following toxicities during Lead-in/Cycle 1 (Day -7 through Day 28) was considered a DLT if judged by the investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen (ENTO, VCR, DEX, institutional standard CNS prophylaxis): * Grade 4 (or higher) non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care * Any Grade 3 non-hematologic laboratory value if: * Medical intervention was required to treat, or * The abnormality led to hospitalization, or * The abnormality persisted for \> 1 week * Grade 4 Neutropenia (absolute neutrophil count \[ANC\] \< 500 /μL) persistent for greater than 14 days or associated with febrile neutropenia * Grade 4 thrombocytopenia (platelets \< 25,000/μL) persisting for greater than 14 days (or greater than 25,000 /μL, but requiring prophylactic platelet transfusion to maintain this level)

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

30 participants

Primary outcome timeframe

ENTO Lead-in and Cycle 1 (Day -7 through Day 28)

Results posted on

2020-01-02

Participant Flow

Participants were enrolled at study sites in Germany, Canada, and United States. The first participant was screened on 06 May 2015. The last study visit occurred on 17 December 2018.

42 participants were screened.

Participant milestones

Participant milestones
Measure	ENTO 200 mg + VCR 0.5 mg Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response \[PR\]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Overall Study STARTED	5	8	7	10
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	5	8	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	ENTO 200 mg + VCR 0.5 mg Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response \[PR\]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Overall Study Adverse Event	0	0	1	0
Overall Study Death	5	5	3	8
Overall Study Progressive Disease	0	0	1	1
Overall Study Study Terminated by Sponsor	0	0	2	1
Overall Study Withdrawal by Subject	0	1	0	0
Overall Study Enrolled but Never Treated	0	2	0	0

Baseline Characteristics

Participants in Full Analysis Set (all participants who received at least 1 dose of study treatment) were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ENTO 200 mg + VCR 0.5 mg n=5 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg n=8 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg n=7 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg n=10 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	Total n=30 Participants Total of all reporting groups
Age, Continuous	46.8 years STANDARD_DEVIATION 16.93 • n=5 Participants • Participants in Full Analysis Set (all participants who received at least 1 dose of study treatment) were analyzed.	51.7 years STANDARD_DEVIATION 17.72 • n=6 Participants • Participants in Full Analysis Set (all participants who received at least 1 dose of study treatment) were analyzed.	47.4 years STANDARD_DEVIATION 9.68 • n=7 Participants • Participants in Full Analysis Set (all participants who received at least 1 dose of study treatment) were analyzed.	52.7 years STANDARD_DEVIATION 19.66 • n=10 Participants • Participants in Full Analysis Set (all participants who received at least 1 dose of study treatment) were analyzed.	50.1 years STANDARD_DEVIATION 16.04 • n=28 Participants • Participants in Full Analysis Set (all participants who received at least 1 dose of study treatment) were analyzed.
Sex: Female, Male Female	5 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	4 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	2 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	3 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	14 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Sex: Female, Male Male	0 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	2 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	5 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	7 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	14 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Race · Asian	1 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	2 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Race · Black	0 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Race · White	4 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	5 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	5 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	10 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	24 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Race · Not Permitted	0 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	1 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	2 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	2 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	5 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	10 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	4 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	3 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	5 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	5 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	17 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Race/Ethnicity, Customized Ethnicity · Not Permitted	0 Participants n=5 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=6 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=7 Participants • Participants in Full Analysis Set were analyzed.	0 Participants n=10 Participants • Participants in Full Analysis Set were analyzed.	1 Participants n=28 Participants • Participants in Full Analysis Set were analyzed.
Region of Enrollment Canada	0 Participants n=5 Participants	1 Participants n=8 Participants	0 Participants n=7 Participants	0 Participants n=10 Participants	1 Participants n=30 Participants
Region of Enrollment United States	5 Participants n=5 Participants	7 Participants n=8 Participants	6 Participants n=7 Participants	9 Participants n=10 Participants	27 Participants n=30 Participants
Region of Enrollment Germany	0 Participants n=5 Participants	0 Participants n=8 Participants	1 Participants n=7 Participants	1 Participants n=10 Participants	2 Participants n=30 Participants

PRIMARY outcome

Timeframe: ENTO Lead-in and Cycle 1 (Day -7 through Day 28)

Population: DLT Analysis Set included all participant in the Safety Analysis Set (all participants who received at least 1 dose of study treatment) who met at least one of the following criteria: received at least 21 days of ENTO, \> 50% of planned total dose of VCR and DEX, or experienced a DLT during the DLT assessment window.

Outcome measures

Outcome measures
Measure	ENTO 200 mg + VCR 0.5 mg n=3 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg n=3 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg n=6 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg n=7 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)	33.3 percentage of participants	0 percentage of participants	16.7 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: End of Induction (Cycle 2, Day 28)

Population: The Full Analysis Set included all participants who received at least 1 dose of study treatment.

Assessment of clinical response was made according to National Comprehensive Cancer Network (NCCN) guidelines on acute lymphoblastic leukemia (ALL) Version 2, 2016. CR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * Trilineage hematopoiesis (TLH) and \< 5% blasts in bone marrow aspirate. * ANC \> 1000/μL. * Platelets \> 100,000/μL.

Outcome measures

Outcome measures
Measure	ENTO 200 mg + VCR 0.5 mg n=5 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg n=6 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg n=7 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg n=10 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Percentage of Participants With Complete Remission (CR) at the End of Induction	20.0 percentage of participants	33.3 percentage of participants	14.3 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: End of Induction (Cycle 2, Day 28)

Population: Participants in the Full Analysis Set were analyzed.

Assessment of clinical response was made according to NCCN guidelines on ALL Version 2, 2016. Overall remission included CR and complete remission with incomplete hematologic recovery (CRi). CR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * TLH and \< 5% blasts in bone marrow aspirate. * ANC \> 1000/μL. * Platelets \> 100,000/μL. CRi required all criteria for CR except platelet count and/or ANC: * Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL

Outcome measures

Outcome measures
Measure	ENTO 200 mg + VCR 0.5 mg n=5 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg n=6 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg n=7 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg n=10 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Percentage of Participants With Overall Remission at the End of Induction	20.0 percentage of participants	33.3 percentage of participants	14.3 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: End of Induction (Cycle 2, Day 28)

Population: Participants in the Full Analysis Set were analyzed.

PR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * TLH and bone marrow may contain ≥ 5% but less than 25% blast morphology. * ANC \> 1000/μL. * Platelets \> 100,000/μL.

Outcome measures

Outcome measures
Measure	ENTO 200 mg + VCR 0.5 mg n=5 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg n=6 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg n=7 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg n=10 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Percentage of Participants With Partial Response (PR) at the End of Induction	0.0 percentage of participants	0.0 percentage of participants	14.3 percentage of participants	10.0 percentage of participants

SECONDARY outcome

Timeframe: End of Induction (Cycle 2, Day 28)

Population: Participants in the Full Analysis Set were analyzed.

Overall response included CR, CRi, and PR. CR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * TLH and \< 5% blasts in bone marrow aspirate. * ANC \> 1000/μL. * Platelets \> 100,000/μL. CRi required all criteria for CR except platelet count and/or ANC: * Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL PR required all criteria for CR except for bone marrow blasts: * bone marrow may contain ≥ 5% but less than 25% blast morphology

Outcome measures

Outcome measures
Measure	ENTO 200 mg + VCR 0.5 mg n=5 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 0.5 mg n=6 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 1.0 mg n=7 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.	ENTO 400 mg + VCR 2.0 mg n=10 Participants Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Percentage of Participants With Overall Response at the End of Induction	20.0 percentage of participants	33.3 percentage of participants	28.6 percentage of participants	10.0 percentage of participants

Adverse Events

ENTO 200 mg + VCR 0.5 mg

Serious events: 5 serious events

Other events: 5 other events

Deaths: 5 deaths

ENTO 400 mg + VCR 0.5 mg

Serious events: 4 serious events

Other events: 5 other events

Deaths: 5 deaths

ENTO 400 mg + VCR 1.0 mg

Serious events: 5 serious events

Other events: 6 other events

Deaths: 5 deaths

ENTO 400 mg + VCR 2.0 mg

Serious events: 6 serious events

Other events: 7 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER