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

Kronos Bio, Inc.0 sites180 target enrollmentSeptember 20, 2021

ConditionsAcute Myeloid Leukemia MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864 Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Acute Myeloid Leukemia
Sponsor: Kronos Bio, Inc.
Enrollment: 180
Status: Active, not recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

September 20, 2021

End Date

TBD

Last Updated

4 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Kronos Bio, Inc.

Eligibility Criteria

Inclusion Criteria

•1\. Adults 18 to 75 years with previously untreated de novo AML, AML with MDS features, or therapy\-related AML.
•2\. NPM1\-mutated disease documented in a local or the Sponsor’s central testing facility.
•Note: Subjects with concurrent FLT3 mutation but without access to midostaurin (eg, either for lack of health authority approval or reimbursement) may also enroll; subjects with a concurrent FLT3 mutation will not be allowed to receive a FLT3 inhibitor at any time during the study treatment period.
•Note: Subjects with local test results for NPM1\-m (and/or FLT3 mutational status) may enroll, provided appropriate samples are sent to the Sponsor’s central testing facility for NPM1\-m companion diagnostic development (see Section 4\.1\).
•3\.Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0, 1, or 2\.
•4\.Adequate hepatic and renal function defined as:
•a.Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2\.5 times the upper limit of normal (ULN), except those with hepatic involvement by AML, as documented by either computed tomography (CT) or ultrasound, in whom levels of AST and ALT \< 5 times ULN are acceptable; total bilirubin \< 1\.5 times ULN unless elevated due to Gilbert’s Disease or hemolysis.
•b.Calculated creatinine clearance \> 40 mL/min or serum creatinine \< 1\.5 times ULN.
•5\.Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) \= 1\.5 x ULN unless receiving therapeutic anticoagulation. Note: Transition from a Vitamin K or Factor Xa antagonist to a low\-molecular weight heparin preparation is recommended prior to the start of induction chemotherapy (see Appendix 8 for guidelines on anticoagulation management).
•6\.Left ventricular ejection fraction \= 45% confirmed by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan.

Exclusion Criteria

•1\.Isolated myeloid sarcoma (ie, participants must have peripheral blood and/or bone marrow involvement by AML) or acute promyelocytic leukemia.
•2\.Known central nervous system (CNS) involvement with leukemia.
•3\.Active infection with hepatitis B, C, or known human immunodeficiency virus (HIV).
•Note: Subjects who are positive for hepatitis B surface antigen (HBsAg) are ineligible. Those who are seropositive for hepatitis B core antibody (anti\-HBc) may enroll but must agree to receive hepatitis B virus (HBV) prophylaxis during the study treatment period and undergo regular surveillance for HBV reactivation at least once every 3 months. Subjects who have received curative therapy for prior HCV infection and who are seropositive for hepatitis C antibody (anti\-HCV), may enroll, however must undergo regular surveillance monitoring for HCV reactivation.
•4\.Known active coronavirus disease 2019 (COVID\-19\) either symptomatic or asymptomatic, as determined by nasopharyngeal swab for severe acute respiratory syndrome (SARS) coronavirus 2 (SARS CoV\-2\) RNA or antigen.
•Note: Subjects with a history of SARS\-CoV\-2 nasopharyngeal carriage (either with or without symptoms), who have subsequently tested negative on follow\-up nasopharyngeal swab and are without signs or symptoms of COVID\-19 may enroll. Subjects who are fully vaccinated against SARS\-CoV\-2 may enroll.
•5\.Disseminated intravascular coagulation with active bleeding or signs of thrombosis.
•6\.History of prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
•7\.History of non\-myeloid malignancy except for the following: adequately treated localized basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy (which may be continued while on study) and with normal prostate specific antigen for \> 1 year prior to start of study therapy; or any other cancer that has been in complete remission without treatment for \= 3 years prior to enrollment.
•Note: Subjects who are on adjuvant hormonal therapy and \= 3 years from definitive therapy for their primary tumor are eligible to enroll.