A Phase 2, Randomized, Biomarker-driven, Clinical Study in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) with an Exploratory Arm in Patients with Newly Diagnosed High-Risk AML and ExploratoryArms with Varying Levels of MCL-1 Dependence

Tolero Pharmaceuticals, Inc.0 sites104 target enrollmentJuly 19, 2017

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Relapsed/Refractory Acute Myeloid Leukemia (AML) with MCL-1 dependence of =40% demonstrated by mitochondrial profiling. Newly diagnosed high-risk (NDHR) AML with MCL-1 dependence of = 40% demonstrated by mitochondrial profiling.Relapsed or primary refractory AML with varying levels of MCL 1 dependence demonstrated by mitochondrial profiling.
Sponsor: Tolero Pharmaceuticals, Inc.
Enrollment: 104
Status: Active, not recruiting
Last Updated: last year

No summary available.

Registry

who.int

Start Date

July 19, 2017

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Sex

All

Sponsor

•During Prescreening:
•1\.Be between the ages of \=18 and \=65 years
•2\.Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria excluding acute promyelocytic leukemia (APL\-M3\) with a bone marrow of \>5% blasts based on histology or flow cytometry
•3\.Be in first relapse (within 24 months of CR) or have primary refractory AML (no CR or CRi after 2 cycles of intensive anthracycline/cytarabine ± etoposide or cladribine induction) or have NDHR AML as defined in this protocol (see Section 4\.4\.4\)
•4\.Demonstrate MCL\-1 dependence of \=40% by mitochondrial profiling in bone marrow, 30 \- \<40% for MCL\-1 Dependency Exploratory Arm A, 15% \- \<30% (MCL 1 Dependency Exploratory Arm B), or 0 \- \<15% (MCL\-1 Dependency Exploratory Arm C).
•During Screening:
•5\. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) \=2
•6\. Have a serum creatinine level \=1\.8 mg/dL
•7\. Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level \=5 times upper limit of normal (ULN)
•8\. Have a total bilirubin level \=2\.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)

•1\. Received more than 2 cycles of induction therapy for AML. Investigational agents as part of front\-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see \#5 below).
•2\. Received any previous treatment with alvocidib or any other CDK inhibitor
•3\. Received a hematopoietic stem cell transplant within the previous 2 months
•4\. Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days
•5\. Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.
•6\. Received \>360 mg/m2 equivalents of daunorubicin
•7\. Have a peripheral blast count of \>30,000/mm3 (may use hydroxyurea as in \#5 above)
•8\. Received antileukemic therapy within the last 3 weeks (with the exception of hydroxyurea or if the patient has definite refractory disease). Refractory patients who received therapy within the last 3 weeks may be eligible with prior approval of the Medical Monitor.
•9\. Diagnosed with acute promyelocytic leukemia (APL, M3\)
•10\. Have active central nervous system (CNS) leukemia