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

NCT ID: NCT02404220

Last Updated: 2020-01-02

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-06

Study Completion Date

2018-12-17

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Vincristine

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

CNS Prophylaxis

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Vincristine

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

CNS Prophylaxis

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Vincristine

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

CNS Prophylaxis

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Entospletinib

Intervention Type DRUG

Vincristine

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

CNS Prophylaxis

Intervention Type DRUG

Interventions

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Entospletinib

Intervention Type DRUG

Vincristine

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

CNS Prophylaxis

Intervention Type DRUG

Other Intervention Names

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GS-9973 ENTO VCR DEX

Eligibility Criteria

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Inclusion Criteria

* Adults with ALL in need of treatment

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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City of Hope

Duarte, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

University of California San Diego (UCSD)

San Diego, California, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Memorial Sloan-Kettering

New York, New York, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Bon Secour St. Francis Hospital

Greenville, South Carolina, United States

Site Status

University of WA

Seattle, Washington, United States

Site Status

Princess Margaret

Toronto, Ontario, Canada

Site Status

Medizinische Klinik mit Schwerpunkt Hepatologie & Gastroenterology

Berlin, , Germany

Site Status

Medizinische Klinik und Poliklinik I

Würzburg, , Germany

Site Status

Countries

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United States Canada Germany

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol: Amendment 5

View Document

Other Identifiers

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2015-002768-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-339-1560

Identifier Type: -

Identifier Source: org_study_id

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