Alvocidib Biomarker-driven Phase 2 AML Study

NCT02520011 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: TPI-ALV-201
• Study Type: interventional
• Target: 104
• Locations: 4 countries
• Sites: 38

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.

Conditions

Acute Myeloid Leukemia

Keywords

Refractory AML; Relapsed AML; AML

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate in Patients With Relapsed or Refractory AML

  Complete Remission (CR) rate = Percentage of patients achieving CR after Cycle 1 as defined in Stage 1 by the International Working Group (IWG) Criteria and 2010 European LeukemiaNet (EN) criteria in patients with relapsed or refractory AML with MCL-1 dependence \>30% and in Stage 2 by the 2017 ELN criteria. The study was terminated in January 2020 due to a steady and marked reduction in enrollment. Thus, the efficacy endpoints could not be analyzed. As sufficient efficacy results were not available to analyze patients based on the percentage of MCL-1 dependency the treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received the ACM vs CM regimen and their disease stages at study entry.

  Best response after at least 1 cycle through study completion approximately 4 years

Other Outcomes (1)

• Response to Treatment

  Best response after at least 1 cycle through study completion approximately 4 years

Study Arms (2)

ACM (Stage 1 / Stage 2)

EXPERIMENTAL

A: alvocidib, 30 mg/m2 as a 30 minute intravenous (IV) bolus followed by 60 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3; C: cytarabine (ara-c), 2 gm/m2 by continuous IV infusion over 72 hours on Days 6-8; M: mitoxantrone (mitoxantrone hydrochloride), 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine

Drug: Alvocidib; Drug: Cytarabine; Drug: Mitoxantrone

CM (Stage 2)

ACTIVE COMPARATOR

C: cytarabine (ara-c), 2 gm/m2 by continuous IV infusion over 72 hours on Days 1-3; M: mitoxantrone (mitoxantrone hydrochloride), 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine

Drug: Cytarabine; Drug: Mitoxantrone

Interventions

Alvocidib DRUG

ACM (Stage 1 / Stage 2)

Cytarabine DRUG

Also known as: ara-c

ACM (Stage 1 / Stage 2); CM (Stage 2)

Mitoxantrone DRUG

Also known as: mitoxantrone hydrochloride

ACM (Stage 1 / Stage 2); CM (Stage 2)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≥30% 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 during and for at least 6 months after completion of study therapy.
• Be able to comply with the requirements of the entire study.
• Provide written informed consent prior to any study related procedure.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (38)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

University of California San Diego UCSD

San Diego, California, 92093-2024, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Morristown Cancer Center

Morristown, New Jersey, 07960, United States

Location

Roswell Park Cancer Center Institute

Buffalo, New York, 14263, United States

Location

Hudson Valley Cancer Center

Hawthorne, New York, 10532, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke

Durham, North Carolina, 27710, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

West Penn Allegheny Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

Hospital Regional Universitario de Malaga

Málaga, Malaga, 29010, Spain

Location

Complejo Hospitalario Universitario de Albacete

Albacete, 02006, Spain

Location

Institut Catala d'Oncologia

Badalona, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, Spain

Location

Hospital Universitario Central de Asturias - HUCA

Oviedo, 33011, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

University Hospitals of Wales

Cardiff, Wales, CF10 3NS, United Kingdom

Location

Univ Hospital of Bristol

Bristol, United Kingdom

Location

Guys Hospital St. Thomas

London, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

alvocidib; Cytarabine; Mitoxantrone

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Limitations and Caveats

The protocol underwent a few major amendments to shorten time to complete and allow for an expeditious analysis and reporting of outcomes. The study was terminated early Jan 2020 due to marked decrease in enrollment and thus could not reach all of its efficacy endpoints. Only select analyses could be performed. Treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received ACM or CM regimen and their disease stages at study entry.

Results Point of Contact

• Title: Susan Smith
• Organization: Sumitomo Dainippon Pharma Oncology, Inc.

Susan.smith@sdponcology.com

+1-210-414-7702

Study Officials

• Stephen Anthony, DO

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 11, 2015
• Study Start: March 14, 2016
• Primary Completion: February 12, 2020
• Study Completion: February 12, 2020
• Last Updated: November 15, 2023
• Results First Posted: July 15, 2021

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (26); GB (3); CA (1); ES (8)