Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

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All Drugs and Chemicals

Dexamethasone

Vincristine

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

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.

Entospletinib

CNS Prophylaxis

Gilead Study Director

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.

Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

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)

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)

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.

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

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.

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

Gilead Sciences

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

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 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

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

Age, Continuous

Participants in Full Analysis Set were analyzed.

Sex: Female, Male

Race

Race/Ethnicity, Customized

Ethnicity

Canada

United States

Germany

Region of Enrollment

All Enrolled Analysis Set included all participants who received a study identification number in the study after screening.

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.

Gilead Clinical Study Information Center

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.

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

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

Spots Global Cancer Trial Database for Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Trial Identification

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Interventions

Study Description

Keywords

Eligibility

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