Suspended

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

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What is being tested

Entospletinib

+ Vincristine
+ Dexamethasone
Drug
Who is being recruted

Acute Lymphoblastic Leukemia

Over 18 Years
+6 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: May 2015

See protocol details

Summary

Principal SponsorGilead Sciences
Last updated: January 2, 2020
Sourced from a government-validated database.Claim as a partner
Study start date: May 6, 2015Actual date on which the first participant was enrolled.

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.

Official TitleA 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) 
Principal SponsorGilead Sciences
Last updated: January 2, 2020
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
30 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are assigned to groups based on specific criteria, such as their medical history or a doctor's recommendation. This approach ensures that treatments are given to those who may benefit the most, based on known factors.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants receive treatments one after another in a pre-planned sequence. The next treatment may depend on how the participant responds to the previous one.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Acute Lymphoblastic Leukemia
Criteria
2 inclusion criteria required to participate
Adults with ALL in need of treatment
ey
4 exclusion criteria prevent from participating
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
ote: Other protocol defined Inclusion/ Exclusion criteria may apply

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
4 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
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 II
Experimental
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 III
Experimental
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 IV
Experimental
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.
Study Objectives
Primary Objectives

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 Objectives

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

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 13 locations
Suspended
City of HopeDuarte, United StatesSee the location
Suspended
UCLALos Angeles, United States
Suspended
UC Irvine Medical CenterOrange, United States
Suspended
University of California San Diego (UCSD)San Diego, United States
Suspended13 Study Centers