Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Sponsor
Gilead Sciences (Industry)
Overall Status
Terminated
CT.gov ID
NCT02404220
Collaborator
(none)
30
13
4
43.4
2.3
0.1
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the safety of entospletinib in combination with vincristine (VCR), and dexamethasone (DEX) in adults with previously treated relapsed or refractory B-cell lineage acute lymphoblastic leukemia (ALL).
This is a dose escalation study in which after 2 induction cycles participants may be put on maintenance for up to 36 cycles if they have obtained clinical benefit from the treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study Evaluating the Safety and Efficacy of Entospletinib (GS-9973) With Vincristine and Dexamethasone in Adult Subjects With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Actual Study Start Date
:
May 6, 2015
Actual Primary Completion Date
:
Nov 16, 2018
Actual Study Completion Date
:
Dec 17, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Entospletinib
Other Names:
Drug: Vincristine
Other Names:
Drug: Dexamethasone
Other Names:
Drug: CNS Prophylaxis
|
| Experimental: 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. |
Drug: Entospletinib
Other Names:
Drug: Vincristine
Other Names:
Drug: Dexamethasone
Other Names:
Drug: CNS Prophylaxis
|
| Experimental: 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. |
Drug: Entospletinib
Other Names:
Drug: Vincristine
Other Names:
Drug: Dexamethasone
Other Names:
Drug: CNS Prophylaxis
|
| Experimental: 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. |
Drug: Entospletinib
Other Names:
Drug: Vincristine
Other Names:
Drug: Dexamethasone
Other Names:
Drug: CNS Prophylaxis
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [ENTO Lead-in and Cycle 1 (Day -7 through Day 28)]
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)
Secondary Outcome Measures
- Percentage of Participants With Complete Remission (CR) at the End of Induction [End of Induction (Cycle 2, Day 28)]
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.
- Percentage of Participants With Overall Remission at the End of Induction [End of Induction (Cycle 2, Day 28)]
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
- Percentage of Participants With Partial Response (PR) at the End of Induction [End of Induction (Cycle 2, Day 28)]
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.
- Percentage of Participants With Overall Response at the End of Induction [End of Induction (Cycle 2, Day 28)]
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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
- Adults with ALL in need of treatment
Key Exclusion Criteria:
-
Diagnosis of Burkitt's Leukemia, or lymphoid blast crisis of chronic myelogenous leukemia (CML)
-
History of myelodysplastic syndrome or solid organ transplantation
-
Prior allogeneic bone marrow progenitor cell transplant within 100 days or on active immunosuppression for graft versus host disease (GVHD) treatment or prophylaxis within 28 days prior to enrollment
Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | UCLA | Los Angeles | California | United States | 90095 |
| 3 | UC Irvine Medical Center | Orange | California | United States | 92608 |
| 4 | University of California San Diego (UCSD) | San Diego | California | United States | 92093 |
| 5 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 6 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 7 | Memorial Sloan-Kettering | New York | New York | United States | 10021 |
| 8 | The Ohio State University | Columbus | Ohio | United States | 43210 |
| 9 | Bon Secour St. Francis Hospital | Greenville | South Carolina | United States | 29601 |
| 10 | University of WA | Seattle | Washington | United States | 98109 |
| 11 | Princess Margaret | Toronto | Ontario | Canada | |
| 12 | Medizinische Klinik mit Schwerpunkt Hepatologie & Gastroenterology | Berlin | Germany | 12200 | |
| 13 | Medizinische Klinik und Poliklinik I | Wurzburg | Germany |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02404220
Other Study ID Numbers:
- GS-US-339-1560
- 2015-002768-18
First Posted:
Mar 31, 2015
Last Update Posted:
Jan 2, 2020
Last Verified:
Dec 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Gilead Sciences
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 42 participants were screened. |
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Period Title: Overall Study | ||||
| STARTED | 5 | 8 | 7 | 10 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 5 | 8 | 7 | 10 |
Baseline Characteristics
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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 of all reporting groups |
| Overall Participants | 5 | 8 | 7 | 10 | 30 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
46.8
(16.93)
|
51.7
(17.72)
|
47.4
(9.68)
|
52.7
(19.66)
|
50.1
(16.04)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
5
100%
|
4
50%
|
2
28.6%
|
3
30%
|
14
46.7%
|
| Male |
0
0%
|
2
25%
|
5
71.4%
|
7
70%
|
14
46.7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Asian |
1
20%
|
0
0%
|
1
14.3%
|
0
0%
|
2
6.7%
|
| Black |
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
1
3.3%
|
| White |
4
80%
|
5
62.5%
|
5
71.4%
|
10
100%
|
24
80%
|
| Not Permitted |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
3.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Hispanic or Latino |
1
20%
|
2
25%
|
2
28.6%
|
5
50%
|
10
33.3%
|
| Not Hispanic or Latino |
4
80%
|
3
37.5%
|
5
71.4%
|
5
50%
|
17
56.7%
|
| Not Permitted |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
3.3%
|
| Region of Enrollment (Count of Participants) | |||||
| Canada |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
3.3%
|
| United States |
5
100%
|
7
87.5%
|
6
85.7%
|
9
90%
|
27
90%
|
| Germany |
0
0%
|
0
0%
|
1
14.3%
|
1
10%
|
2
6.7%
|
Outcome Measures
| Title | Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | 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) |
| Time Frame | ENTO Lead-in and Cycle 1 (Day -7 through Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 3 | 3 | 6 | 7 |
| Number [percentage of participants] |
33.3
666%
|
0
0%
|
16.7
238.6%
|
0
0%
|
| Title | Percentage of Participants With Complete Remission (CR) at the End of Induction |
|---|---|
| Description | 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. |
| Time Frame | End of Induction (Cycle 2, Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set included all participants who received at least 1 dose of study treatment. |
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 6 | 7 | 10 |
| Number [percentage of participants] |
20.0
400%
|
33.3
416.3%
|
14.3
204.3%
|
0
0%
|
| Title | Percentage of Participants With Overall Remission at the End of Induction |
|---|---|
| Description | 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 |
| Time Frame | End of Induction (Cycle 2, Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 6 | 7 | 10 |
| Number [percentage of participants] |
20.0
400%
|
33.3
416.3%
|
14.3
204.3%
|
0.0
0%
|
| Title | Percentage of Participants With Partial Response (PR) at the End of Induction |
|---|---|
| Description | 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. |
| Time Frame | End of Induction (Cycle 2, Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 6 | 7 | 10 |
| Number [percentage of participants] |
0.0
0%
|
0.0
0%
|
14.3
204.3%
|
10.0
100%
|
| Title | Percentage of Participants With Overall Response at the End of Induction |
|---|---|
| Description | 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 |
| Time Frame | End of Induction (Cycle 2, Day 28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set were analyzed. |
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 6 | 7 | 10 |
| Number [percentage of participants] |
20.0
400%
|
33.3
416.3%
|
28.6
408.6%
|
10.0
100%
|
Adverse Events
| Time Frame | Adverse Events: First dose date up to maximum 18 months; All-Cause Mortality: First dose date up to maximum 3.5 years | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety Analysis Set included all participants who received at least 1 dose of study treatment. | |||||||
| Arm/Group Title | ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg | ||||
| Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 5/6 (83.3%) | 5/7 (71.4%) | 9/10 (90%) | ||||
Serious Adverse Events |
||||||||
| ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 4/6 (66.7%) | 5/7 (71.4%) | 6/10 (60%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 3/5 (60%) | 2/6 (33.3%) | 0/7 (0%) | 1/10 (10%) | ||||
| Cardiac disorders | ||||||||
| Cardiac failure | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Cardiac failure congestive | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Eye disorders | ||||||||
| Visual impairment | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Ileus | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Nausea | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Vomiting | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Cellulitis | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Device related infection | 0/5 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Fungaemia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Oesophageal candidiasis | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Pneumonia | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Sepsis | 0/5 (0%) | 1/6 (16.7%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Sinusitis | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Sinusitis fungal | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Staphylococcal bacteraemia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Hip fracture | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Investigations | ||||||||
| Blood bilirubin increased | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Tumour lysis syndrome | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Nervous system disorders | ||||||||
| Aphasia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Cerebrovascular accident | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Haemorrhage intracranial | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Headache | 2/5 (40%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Psychiatric disorders | ||||||||
| Confusional state | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Mental status changes | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| ENTO 200 mg + VCR 0.5 mg | ENTO 400 mg + VCR 0.5 mg | ENTO 400 mg + VCR 1.0 mg | ENTO 400 mg + VCR 2.0 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 5/6 (83.3%) | 6/7 (85.7%) | 7/10 (70%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/5 (40%) | 2/6 (33.3%) | 0/7 (0%) | 3/10 (30%) | ||||
| Febrile neutropenia | 2/5 (40%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Haemolysis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Leukocytosis | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Lymphadenopathy | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Neutropenia | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 1/10 (10%) | ||||
| Pancytopenia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Thrombocytopenia | 2/5 (40%) | 1/6 (16.7%) | 0/7 (0%) | 1/10 (10%) | ||||
| Cardiac disorders | ||||||||
| Pericardial effusion | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Sinus tachycardia | 1/5 (20%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear discomfort | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Endocrine disorders | ||||||||
| Cushingoid | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Eye disorders | ||||||||
| Dry eye | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Eye haemorrhage | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 0/5 (0%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Abdominal pain | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Abdominal pain upper | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Cheilitis | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Constipation | 1/5 (20%) | 1/6 (16.7%) | 1/7 (14.3%) | 2/10 (20%) | ||||
| Diarrhoea | 3/5 (60%) | 3/6 (50%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Dyspepsia | 0/5 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Gastrooesophageal reflux disease | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Haematochezia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Haemorrhoids | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Mouth haemorrhage | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Nausea | 4/5 (80%) | 4/6 (66.7%) | 4/7 (57.1%) | 2/10 (20%) | ||||
| Oral disorder | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Rectal haemorrhage | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Stomatitis | 1/5 (20%) | 2/6 (33.3%) | 0/7 (0%) | 0/10 (0%) | ||||
| Vomiting | 2/5 (40%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Catheter site erythema | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Catheter site haemorrhage | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Catheter site pain | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Chest discomfort | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Chills | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Crepitations | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Fatigue | 3/5 (60%) | 2/6 (33.3%) | 2/7 (28.6%) | 3/10 (30%) | ||||
| Feeling cold | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Generalised oedema | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Influenza like illness | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Injection site bruising | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Malaise | 0/5 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Mucosal inflammation | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Oedema peripheral | 2/5 (40%) | 2/6 (33.3%) | 0/7 (0%) | 1/10 (10%) | ||||
| Pain | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Puncture site pain | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Pyrexia | 1/5 (20%) | 0/6 (0%) | 3/7 (42.9%) | 0/10 (0%) | ||||
| Immune system disorders | ||||||||
| Cytokine release syndrome | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Clostridium difficile colitis | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Escherichia urinary tract infection | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Folliculitis | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Gastroenteritis norovirus | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Influenza | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Oral herpes | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Post procedural infection | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Pyelonephritis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Rhinovirus infection | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Sinusitis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Sinusitis fungal | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Viral upper respiratory tract infection | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Fall | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Procedural pain | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 1/10 (10%) | ||||
| Aspartate aminotransferase increased | 2/5 (40%) | 1/6 (16.7%) | 1/7 (14.3%) | 2/10 (20%) | ||||
| Blood bilirubin increased | 2/5 (40%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Blood immunoglobulin G decreased | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Escherichia test positive | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| International normalised ratio increased | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Lymphocyte count decreased | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 2/10 (20%) | ||||
| Neutrophil count decreased | 1/5 (20%) | 1/6 (16.7%) | 1/7 (14.3%) | 3/10 (30%) | ||||
| Platelet count decreased | 0/5 (0%) | 1/6 (16.7%) | 2/7 (28.6%) | 2/10 (20%) | ||||
| Staphylococcus test positive | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Weight decreased | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| White blood cell count decreased | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 3/10 (30%) | ||||
| White blood cell count increased | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/5 (20%) | 0/6 (0%) | 2/7 (28.6%) | 1/10 (10%) | ||||
| Dehydration | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Fluid retention | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Gout | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Hyperglycaemia | 3/5 (60%) | 0/6 (0%) | 1/7 (14.3%) | 2/10 (20%) | ||||
| Hypermagnesaemia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Hypernatraemia | 2/5 (40%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Hyperuricaemia | 2/5 (40%) | 2/6 (33.3%) | 0/7 (0%) | 1/10 (10%) | ||||
| Hypoalbuminaemia | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Hypocalcaemia | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Hypokalaemia | 4/5 (80%) | 1/6 (16.7%) | 0/7 (0%) | 1/10 (10%) | ||||
| Hypomagnesaemia | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Hyponatraemia | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Hypophosphataemia | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Metabolic acidosis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 2/10 (20%) | ||||
| Back pain | 1/5 (20%) | 1/6 (16.7%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Muscle spasms | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Muscular weakness | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Musculoskeletal pain | 0/5 (0%) | 2/6 (33.3%) | 0/7 (0%) | 0/10 (0%) | ||||
| Myalgia | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Myopathy | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Neck pain | 2/5 (40%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Pain in extremity | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Synovial cyst | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Nervous system disorders | ||||||||
| Carotid arteriosclerosis | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Dizziness | 2/5 (40%) | 0/6 (0%) | 2/7 (28.6%) | 2/10 (20%) | ||||
| Haemorrhage intracranial | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Headache | 2/5 (40%) | 1/6 (16.7%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Hemiparesis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Lumbar radiculopathy | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Memory impairment | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Neuropathy peripheral | 1/5 (20%) | 0/6 (0%) | 3/7 (42.9%) | 1/10 (10%) | ||||
| Paraesthesia | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Peripheral motor neuropathy | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Peripheral sensory neuropathy | 1/5 (20%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Restless legs syndrome | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Seizure | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Tremor | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Product Issues | ||||||||
| Device malfunction | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Anxiety | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Confusional state | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Delirium | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Fear | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Insomnia | 1/5 (20%) | 0/6 (0%) | 2/7 (28.6%) | 4/10 (40%) | ||||
| Irritability | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Restlessness | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/5 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Dysuria | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Haematuria | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Micturition urgency | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Proteinuria | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Urinary tract pain | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Dysfunctional uterine bleeding | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 2/5 (40%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Dyspnoea | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Dyspnoea exertional | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Epistaxis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Hypoxia | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Nasal congestion | 0/5 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Oropharyngeal pain | 1/5 (20%) | 2/6 (33.3%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Productive cough | 1/5 (20%) | 1/6 (16.7%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Respiratory failure | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Rhinorrhoea | 0/5 (0%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Sneezing | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Upper-airway cough syndrome | 0/5 (0%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Wheezing | 0/5 (0%) | 1/6 (16.7%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Ecchymosis | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Hyperhidrosis | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Night sweats | 0/5 (0%) | 2/6 (33.3%) | 0/7 (0%) | 0/10 (0%) | ||||
| Purpura | 0/5 (0%) | 0/6 (0%) | 0/7 (0%) | 1/10 (10%) | ||||
| Rash | 2/5 (40%) | 1/6 (16.7%) | 0/7 (0%) | 0/10 (0%) | ||||
| Rash maculo-papular | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Swelling face | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 1/5 (20%) | 0/6 (0%) | 1/7 (14.3%) | 1/10 (10%) | ||||
| Hot flush | 0/5 (0%) | 0/6 (0%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Hypertension | 1/5 (20%) | 0/6 (0%) | 2/7 (28.6%) | 0/10 (0%) | ||||
| Hypotension | 1/5 (20%) | 1/6 (16.7%) | 1/7 (14.3%) | 0/10 (0%) | ||||
| Pallor | 1/5 (20%) | 0/6 (0%) | 0/7 (0%) | 0/10 (0%) | ||||
Limitations/Caveats
Due to the low response rate observed with ENTO + VCR + DEX in adults with relapsed or refractory B-ALL, the sponsor decided not to proceed with Phase 2 (dose-expansion) and the cohort was subsequently closed with no participant enrolled.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Results Point of Contact
| Name/Title | Gilead Clinical Study Information Center |
|---|---|
| Organization | Gilead Sciences |
| Phone | 1-833-445-3230 (GILEAD-0) |
| GileadClinicalTrials@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02404220
Other Study ID Numbers:
- GS-US-339-1560
- 2015-002768-18
First Posted:
Mar 31, 2015
Last Update Posted:
Jan 2, 2020
Last Verified:
Dec 1, 2019