Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Daunorubicin

Idarubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Participants received intensive chemotherapy (cytarabine and anthracycline \[daunorubicin or idarubicin\]) in combination with entospletinib (ENTO).

Participants received intensive chemotherapy (cytarabine and anthracycline \[daunorubicin or idarubicin\]) in combination with the matching placebo.

Entospletinib

Placebo

Either daunorubicin or idarubicin was administered via slow intravenous (IV) push

Anthracycline

The primary objective of this study is to evaluate the efficacy of entospletinib (ENTO) compared to placebo when added to chemotherapy in previously untreated nucleophosmin-1 mutated (NPM1-m) acute myeloid leukemia (AML), as defined by the rate of molecularly defined measurable residual disease (MRD).

This is a multi-center, international, double-blind, placebo-controlled study in previously untreated participants with acute myeloid leukemia (AML) harboring nucleophosmin-1 (NPM1) mutations. Upon fulfillment of all eligibility criteria, participants were randomized 1:1 to receive intensive chemotherapy in combination with either the spleen tyrosine kinase (SYK) inhibitor entospletinib (ENTO), or placebo. The study consisted of Screening, Induction, Consolidation, End-of-Treatment, and Long-term Follow-up phases.

Entospletinib Plus Intensive Induction/Consolidation Chemotherapy in Newly Diagnosed NPM1-mutated AML

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Entospletinib in Combination With Intensive Induction and Consolidation Chemotherapy in Adults With Newly Diagnosed Nucleophosmin 1-mutated Acute Myeloid Leukemia

MRD negative CR requires CR as defined by the European Leukemia Network (ELN) 2017 criteria (with minor modification for neutrophil and platelet count thresholds as defined by International Working Group \[IWG\]) as assessed by study site investigators, and MRD negativity (\<0.01%) in bone marrow as measured by a molecular nucleophosmin-1 mutated (NPM1-m) assay (eg, next generation sequencing) in a central laboratory upon recovery of peripheral blood counts following completion of 2 cycles of chemotherapy, no later than Day 42 of Cycle 2.

EFS is defined as the time from randomization to the earliest occurrence of induction treatment failure, relapse from CR, or death from any cause. Induction treatment failure is failure to achieve morphological CR after completion of the last cycle of induction chemotherapy (no later than Day 42 of the last cycle of induction).

RFS is defined as the time from CR until relapse or death from any cause as assessed by study site investigators.

OS is defined as the time from randomization until death from any cause.

CR as defined by ELN 2017 criteria (with minor modification for neutrophil and platelet count thresholds as defined by IWG) as assessed by study site investigators.

A TEAE is any untoward medical occurrence in a clinical study participant, beginning or worsening from Cycle 1, Day 1 through 30 days following study treatment completion, temporarily associated with the use of treatment, whether or not considered related to the study treatment. TEAEs were recorded according to the most current version of the Medical Dictionary for Regulatory Activities (MedDRA).

Clinically significant changes in safety laboratory assessments, electrocardiograms, echocardiogram / multi-gated acquisition scans and Eastern Cooperative Oncology Group performance status findings, as assessed by the Investigator, were recorded as TEAEs.

Kronos Bio

A TEAE is any untoward medical occurrence in a clinical study participant, beginning or worsening from Cycle 1, Day 1 through 30 days following study treatment completion, temporarily associated with the use of treatment, whether or not considered related to the study treatment. TEAEs were recorded according to the most current version of the Medical Dictionary for Regulatory Activities (MedDRA).

Participants received ENTO twice daily (BID), along with intensive chemotherapy (cytarabine and anthracycline) by continuous intravenous (IV) infusion (cytarabine) or slow IV push (anthracycline).

ENTO

Participants received placebo BID, along with intensive chemotherapy (cytarabine and anthracycline) by continuous intravenous (IV) infusion (cytarabine) or slow IV push (anthracycline).

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Early termination was due to significant unforeseen challenges associated with global enrollment of participants with genetically-defined, newly diagnosed, AML who are candidates for intensive induction therapy and other challenges associated with post-COVID impacts.

VP, Corporate Affairs

Participants received ENTO BID, along with intensive chemotherapy (cytarabine and anthracycline) by continuous IV infusion (cytarabine) or slow IV push (anthracycline).

Participants received placebo, BID, along with intensive chemotherapy (cytarabine and anthracycline) by continuous IV infusion (cytarabine) or slow IV push (anthracycline).

Data not collected as the study was terminated early.

Number of Participants With Measurable Residual Disease (MRD) Negative Complete Response (CR) Rate

Participants received ENTO, BID, along with intensive chemotherapy (cytarabine and anthracycline) by continuous IV infusion (cytarabine) or slow IV push (anthracycline).

Event-free Survival (EFS)

Relapse-free Survival (RFS)

Overall Survival (OS)

Intent-to-Treat (ITT) Analysis Set: All participants who were randomized.

Number of Participant With Complete Response (CR) After 2 Cycles of Chemotherapy

Participants received ENTO, BID along with intensive chemotherapy (cytarabine and anthracycline) by continuous IV infusion (cytarabine) or slow IV push (anthracycline).

Participants received placebo BID, along with intensive chemotherapy (cytarabine and anthracycline) by continuous intravenous (IV) infusion (cytarabine) or slow IV push (anthracycline)

Safety Analysis Set: All participants randomized who received at least one dose of study medication.

Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

Participants received ENTO twice daily (BID), along with intensive chemotherapy (cytarabine and anthracycline) by continuous intravenous (IV) infusion (cytarabine) or slow IV push (anthracycline)

Spots Global Cancer Trial Database for ento

Every month we try and update this database with for ento cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ento

Every month we try and update this database with for ento cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ento cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.