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Alvocidib Biomarker-driven Phase 2 AML Study

Trial Status: Active

The purpose of this two-stage Phase 2 study is to assess the clinical response (Complete Remission) of ACM (Alvocidib / Cytarabine / Mitoxantrone) compared to CM (Cytarabine / Mitoxantrone) treatment in refractory or relapsed AML patients with demonstrated MCL-1 dependence of ≥ 40% by mitochondrial profiling in bone marrow.

Inclusion Criteria

  • Be between the ages of ≥18 and ≤65 years
  • 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
  • Be in first relapse (within 24 months of CR) or have failed induction therapy* (no CR or CRi after treatment with an intensive regimen (eg, anthracycline/cytarabine ± etoposide, gemtuzumab ozogamicin, or cladribine). *Induction therapy may involve 1 or 2 cycles of the same regimen. Efficacy assessment of induction therapy must be >21 days from the start of the previous induction cycle.
  • Demonstrate MCL-1 dependence of ≥40% by mitochondrial profiling in bone marrow.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
  • Have a serum creatinine level ≤1.8 mg/dL
  • Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)
  • Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)
  • Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
  • Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry, for the duration of study participation, and for at least 3 months (males) and 6 months (females) after the last dose of study drug.
  • Be able to comply with the requirements of the entire study.
  • Provide written informed consent prior to any study related procedure.

Exclusion Criteria

  • 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).
  • Received any previous treatment with alvocidib or any other CDK inhibitor
  • Received a hematopoietic stem cell transplant within the previous 2 months
  • Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days
  • 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.
  • Received >360 mg/m2 equivalents of daunorubicin
  • Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #5 above)
  • 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.
  • Diagnosed with acute promyelocytic leukemia (APL, M3)
  • Have active central nervous system (CNS) leukemia
  • Have evidence of uncontrolled disseminated intravascular coagulation
  • Have an active, uncontrolled infection
  • Have other life-threatening illness
  • Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
  • Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
  • Are pregnant and/or nursing
  • Have received any live vaccine within 14 days prior to first study drug administration.

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Vlad Kustanovich
Phone: 310-206-5755
San Diego
University of California San Diego
Status: CLOSED_TO_ACCRUAL

Florida

Jacksonville
Mayo Clinic in Florida
Status: ACTIVE
Tampa
Moffitt Cancer Center
Status: ADMINISTRATIVELY_COMPLETE

Illinois

Chicago
Northwestern University
Status: CLOSED_TO_ACCRUAL

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Karen Parrott
Phone: 319-353-6347

Kansas

Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: ACTIVE

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Jacqueline Greer
Phone: 410-614-1329

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Minnesota

Rochester
Mayo Clinic
Status: ACTIVE

Nebraska

Omaha
University of Nebraska Medical Center
Status: ACTIVE

New York

Buffalo
Roswell Park Cancer Institute
Status: CLOSED_TO_ACCRUAL
New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Mark Gerard Frattini
Phone: 212-305-8615

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Joshua F. Zeidner
Phone: 877-668-0683
Durham
Duke University Medical Center
Status: COMPLETED

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Columbus
Ohio State University Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

South Carolina

Charleston
Medical University of South Carolina
Status: IN_REVIEW

Texas

Houston
M D Anderson Cancer Center
Status: COMPLETED
Contact: Carol Bivins
Phone: 713-794-4460

In Stage 1 of the study, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 40% by mitochondrial profiling in bone marrow will receive treatment with ACM. In Stage 2, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 40% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Tolero Pharmaceuticals, Inc.

  • Primary ID TPI-ALV-201
  • Secondary IDs NCI-2015-02082
  • Clinicaltrials.gov ID NCT02520011