Clinical trial NCT02520011: Alvocidib Biomarker-driven Phase 2 AML Study
Official title: Phase 2, Randomized, Biomarker-driven Clinical Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With MCL-1 Dependence ≥30%
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Refractory AML
Relapsed AML
AML
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-11
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 ≥ 30% by mitochondrial profiling in bone marrow.

Detailed description: In Stage 1 of the study, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow will receive treatment with ACM.

In Stage 2, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM.

Eligibility criteria: Inclusion Criteria:

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 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.
4. Demonstrate MCL-1 dependence of ≥30% by mitochondrial profiling in bone marrow.
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)
9. Have a left ventricular ejection fraction (LVEF) \>45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
10. 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 during and for at least 6 months after completion of study therapy.
11. Be able to comply with the requirements of the entire study.
12. Provide written informed consent prior to any study related procedure.

Exclusion Criteria:

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
11. Have evidence of uncontrolled disseminated intravascular coagulation
12. Have an active, uncontrolled infection
13. Have other life-threatening illness
14. Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
15. Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
16. Are pregnant and/or nursing
17. Have received any live vaccine within 14 days prior to first study drug administration.

Primary outcomes:
measure: Complete Response (CR) Rate in Patients With Relapsed or Refractory AML
timeFrame: Best response after at least 1 cycle through study completion approximately 4 years
Secondary outcomes:
Other outcomes:
measure: Response to Treatment
timeFrame: Best response after at least 1 cycle through study completion approximately 4 years
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: San Diego
country: United States
facility: University of California San Diego UCSD
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Cancer Center at Johns Hopkins
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Morristown Cancer Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Center Institute
state: New York
city: Hawthorne
country: United States
facility: Hudson Valley Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: West Penn Allegheny Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
state: Malaga
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias - HUCA
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Cardiff
country: United Kingdom
facility: University Hospitals of Wales
state: Wales
city: Bristol
country: United Kingdom
facility: Univ Hospital of Bristol
city: London
country: United Kingdom
facility: Guys Hospital St. Thomas
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: Stephen Anthony, DO
role: STUDY_DIRECTOR
References: