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Alvocidib Biomarker-driven Phase 2 AML Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02520011
Recruitment Status : Recruiting
First Posted : August 11, 2015
Last Update Posted : May 23, 2019
Information provided by (Responsible Party):
Tolero Pharmaceuticals, Inc.

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 ≥ 40% by mitochondrial profiling in bone marrow.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Alvocidib Drug: Cytarabine Drug: Mitoxantrone Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 79 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2, Randomized, Biomarker-driven Clinical Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With MCL-1 Dependence ≥40%
Actual Study Start Date : March 14, 2016
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: ACM (Stage 1 / Stage 2)
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
Other Name: ara-c

Drug: Mitoxantrone
Other Name: mitoxantrone hydrochloride

Active Comparator: CM (Stage 2)
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
Other Name: ara-c

Drug: Mitoxantrone
Other Name: mitoxantrone hydrochloride

Primary Outcome Measures :
  1. Complete Remission (CR) rate = Percentage of patients achieving CR after Cycle 1 as defined in Stage 1 by the International Working Group Criteria and 2010 European LeukemiaNet (ELN) criteria and in Stage 2 by the 2017 ELN criteria. [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Overall Survival (OS) Rate [ Time Frame: 2 years ]
    Day 1 until death from any cause

  2. Combined CR Rate = Percentage of patients achieving CR, CRi, CRp (CRp is kept in definitions for Combined CR Rate / Combined Remission Rate as Stage-1 patients were assessed by IWG criteria. CRp won't be used for assessing Stage-2 patients.) [ Time Frame: 3 months ]
  3. Combined Response Rate = Percentage of patients achieving CR, CRi, CRp, PR [ Time Frame: 3 months ]
  4. Rate of Stem Cell Transplantation [ Time Frame: 6 months ]
  5. Event-Free Survival [ Time Frame: 2 years ]

Other Outcome Measures:
  1. Mortality [ Time Frame: 30 and 60 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 ≥40% 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 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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02520011

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Contact: Judy Costas, BSN 361-649-9176
Contact: Susan Smith, MS 210-414-7702

  Hide Study Locations
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United States, Arizona
Honor Health Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Kenneth Fulton    480-323-1973   
Principal Investigator: Jeffrey Schriber, MD         
United States, California
University of California Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Bruck Habtemariam, CRC    310-794-0242   
Principal Investigator: Gary Schiller, MD         
University of California San Diego UCSD Terminated
San Diego, California, United States, 92093-2024
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trial Referral Office    855-776-0015      
Principal Investigator: James Foran, MD         
United States, Georgia
Northside Hospital Terminated
Atlanta, Georgia, United States, 30342
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Karen Parrott, RN, BSN    319-353-6347   
Principal Investigator: Carlos Vigil, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Kerry Hepler    913-945-7552   
Principal Investigator: Tara Lin, MD         
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Amanda Woolery    504-842-0275   
Principal Investigator: Andrew Dalovisio, MD         
United States, Maryland
Sidney Kimmel Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Laura Cucci    410-614-5407   
Contact: Brynn Puller    410-955-8880   
Principal Investigator: B. Douglas Smith, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cancer Answer Line    800-865-1125      
Principal Investigator: Dale Bixby, MD         
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Mark Litzow, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Tracy Mathison   
Principal Investigator: Vijaya Bhatt, MD         
United States, New Jersey
Morristown Cancer Center Recruiting
Morristown, New Jersey, United States, 07960
Contact: Mohammad Cherry, MD         
Principal Investigator: Mohammad Cherry, MD         
United States, New York
Roswell Park Cancer Center Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Gretchen Watkins    716-845-1516   
Principal Investigator: Eunice Wang, MD         
Hudson Valley Cancer Center Terminated
Hawthorne, New York, United States, 10532
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Sarah Leach    212-304-5585   
Principal Investigator: Daniel Lee, MD         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Jack Zhang    984-974-8251   
Principal Investigator: Joshua Zeidner, MD         
Duke Terminated
Durham, North Carolina, United States, 27710
East Carolina University Terminated
Greenville, North Carolina, United States, 27858
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Aziz Nazha    216-445-7009   
Principal Investigator: Aziz Nazha, MD         
United States, Pennsylvania
West Penn Allegheny Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Salman Fazal, MD         
Principal Investigator: Salman Fazal, MD         
United States, Texas
Baylor Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Juanita Rendon    214-820-4266   
Principal Investigator: Moshe Levy, MD         
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Carol Bivins    713-794-4460   
Principal Investigator: Jorge Cortes, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Hayden Krause    414-805-0596   
Principal Investigator: Ehab Atallah, MD         
Canada, Ontario
Princess Margaret Cancer Center Terminated
Toronto, Ontario, Canada, M5G 2M9
Institut Catala d'Oncologia Recruiting
Badalona, Spain
Contact: Susana Vives, MD    0034 4978987      
Principal Investigator: Susana Vives, MD         
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Jordi Esteve Reyner, MD    +34 932 275428      
Principal Investigator: Jordi Esteve Reyner, MD         
Hospital San Pedro de Alcantara Recruiting
Cáceres, Spain
Contact: Juan Bergua Burgues, MD    +34 927 621546      
Principal Investigator: Juan Bergua Burgues, MD         
Hospital Universitario Central de Asturias - HUCA Recruiting
Oviedo, Spain, 33011
Contact: Teresa Bernal del Castillo, MD    +34 985 652489      
Principal Investigator: Teresa Bernal del Castillo, MD         
Hospital Clinico Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Contact: Maria Belen Vidriales Vicente, MD    +34 923 291100 ext 55974      
Principal Investigator: Maria Belen Vidriales Vicente, MD         
Hospital Universitari i Politècnic La Fe Recruiting
Valencia, Spain
Contact: Pau Montesinos, MD    +34 96 1244000 ext 411966      
Principal Investigator: Pau Montesinos, MD         
United Kingdom
Univ Hospital of Bristol Recruiting
Bristol, United Kingdom
Contact: Priyanka Mehta, MD    0044 117 342 1119      
Principal Investigator: Priyanka Mehta, MD         
Guys Hospital St. Thomas Recruiting
London, United Kingdom
Contact: Richard Dillon, MD    7969386998      
Principal Investigator: Richard Dillon, MD         
Sponsors and Collaborators
Tolero Pharmaceuticals, Inc.
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Study Director: Stephen Anthony, DO Tolero Pharmaceuticals

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Responsible Party: Tolero Pharmaceuticals, Inc. Identifier: NCT02520011     History of Changes
Other Study ID Numbers: TPI-ALV-201
First Posted: August 11, 2015    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tolero Pharmaceuticals, Inc.:
Refractory AML
Relapsed AML
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Protein Kinase Inhibitors