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. |
ClinicalTrials.gov Identifier: NCT02520011 |
Recruitment Status
:
Recruiting
First Posted
: August 11, 2015
Last Update Posted
: January 16, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Acute Myeloid Leukemia | Drug: Alvocidib Drug: Cytarabine Drug: Mitoxantrone | Phase 2 |
In Stage 1 of the study, all eligible AML patients with demonstrated NOXA BH3 priming of ≥ 40% by mitochondrial profiling in bone marrow will receive treatment with alvocidib, cytarabine and mitoxantrone [ACM ('FLAM') regimen].
In Stage 2, all eligible AML patients with demonstrated NOXA BH3 priming of ≥ 40% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM (cytarabine and mitoxantrone).
In the NDHR exploratory arm, all eligible patients with newly diagnosed high-risk (NDHR) AML with NOXA BH3 priming ≥40% by mitochondrial profiling in bone marrow will receive treatment with ACM.
In the NOXA exploratory arm, all eligible AML patients with demonstrated NOXA BH3 priming of ≥ 30 - 39% by mitochondrial profiling in bone marrow will receive treatment with ACM.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 119 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2, Randomized, Biomarker-driven, Clinical Study on Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With an Exploratory Arm in Patients With Newly Diagnosed High-Risk AML |
Actual Study Start Date : | March 14, 2016 |
Estimated Primary Completion Date : | June 2018 |
Estimated Study Completion Date : | December 2019 |

Arm | Intervention/treatment |
---|---|
Experimental: ACM (Stage 1 / Stage 2)
A: alvocidib (formerly flavopiridol), 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
Other Name: flavopiridol
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
|
Experimental: Exploratory Arm - NDHR
A: alvocidib (formerly flavopiridol), 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
Other Name: flavopiridol
Drug: Cytarabine
Other Name: ara-c
Drug: Mitoxantrone
Other Name: mitoxantrone hydrochloride
|
Experimental: Exploratory Arm - NOXA
A: alvocidib (formerly flavopiridol), 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
Other Name: flavopiridol
Drug: Cytarabine
Other Name: ara-c
Drug: Mitoxantrone
Other Name: mitoxantrone hydrochloride
|
- Complete Remission (CR) rate = Percentage of patients achieving CR [ Time Frame: 3 months ]
- Overall Survival (OS) Rate [ Time Frame: 2 years ]Day 1 until death from any cause
- Combined CR Rate = Percentage of patients achieving CR, CRi, CRp [ Time Frame: 3 months ]
- Combined Response Rate = Percentage of patients achieving CR, CRi, CRp, PR [ Time Frame: 3 months ]
- Rate of Stem Cell Transplantation [ Time Frame: 6 months ]
- Event-Free Survival [ Time Frame: 2 years ]
- Mortality [ Time Frame: 30 and 60 days ]

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.
Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 primary refractory AML (refractory to initial induction therapy using 1 or 2 cycles of intensive anthracycline/cytarabine ± etoposide or cladribine induction) or have newly diagnosed high-risk AML as defined in this protocol.
- Demonstrate NOXA BH3 priming of ≥40% by mitochondrial profiling in bone marrow or 30 - 39% for NOXA Exploratory Arm.
- 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 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.
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.

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 ClinicalTrials.gov identifier (NCT number): NCT02520011
Contact: Judy Costas, BSN | 3616499176 | jcostas@toleropharma.com |
United States, Georgia | |
Northside Hospital | Recruiting |
Atlanta, Georgia, United States, 30342 | |
Contact: Nancy Shegda 404-845-5929 nancy.mccarthy@Northside.com | |
Principal Investigator: Lawrence Morris, MD | |
United States, Iowa | |
University of Iowa | Recruiting |
Iowa City, Iowa, United States, 52242 | |
Contact: Karen Parrott, RN, BSN 319-353-6347 karen-parrott@uiowa.edu | |
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 ctnursenav@kumc.edu | |
Principal Investigator: Tara Lin, MD | |
United States, Louisiana | |
Ochsner Clinic Foundation | Recruiting |
New Orleans, Louisiana, United States, 70121 | |
Contact: Amanda Woolery 504-842-0275 Amanda.woolery@ochsner.org | |
Principal Investigator: Andrew Dalovisio, MD | |
United States, Maryland | |
Sidney Kimmel Cancer Center at Johns Hopkins | Recruiting |
Baltimore, Maryland, United States, 21287 | |
Contact: Seanna Coffin 410-614-2023 scoffin1@jhmi.edu | |
Principal Investigator: B. Douglas Smith, MD | |
United States, New York | |
Hudson Valley Cancer Center | Not yet recruiting |
Hawthorne, New York, United States, 10532 | |
Contact: Kyaw Htun 914-493-8375 khtun@nymc.edu | |
Principal Investigator: Karen Seiter, MD | |
Columbia University Medical Center | Recruiting |
New York, New York, United States, 10032 | |
Contact: Sarah Leach 212-304-5585 sl3971@cumc.columbia.edu | |
Principal Investigator: Mark Frattini, MD | |
United States, North Carolina | |
University of North Carolina | Recruiting |
Chapel Hill, North Carolina, United States, 27599 | |
Contact: Jack Zhang jack_zhang@med.unc.edu | |
Principal Investigator: Joshua Zeidner, MD | |
Duke | Recruiting |
Durham, North Carolina, United States, 27710 | |
Contact: Rachel Stowe 919-681-4769 rachel.stowe@duke.edu | |
Principal Investigator: David Rizzieri, MD | |
East Carolina University | Recruiting |
Greenville, North Carolina, United States, 27858 | |
Contact: Denise Brigham 252-744-4924 brighamd16@ecu.edu | |
Principal Investigator: Darla Liles, MD | |
United States, Texas | |
Baylor Sammons Cancer Center | Recruiting |
Dallas, Texas, United States, 75246 | |
Contact: Amy Solis 214-820-8685 amy.solis@bswhealth.org | |
Principal Investigator: Moshe Levy, MD | |
MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Carol Bivins 713-794-4460 cbibins@mdanderson.org | |
Principal Investigator: Jorge Cortes, MD | |
United States, Wisconsin | |
Medical College of Wisconsin | Recruiting |
Milwaukee, Wisconsin, United States, 53226 | |
Contact: Hayden Krause 414-805-0596 hkrause@mcw.edu | |
Principal Investigator: Ehab Atallah, MD | |
Canada, Ontario | |
Princess Margaret Cancer Center | Recruiting |
Toronto, Ontario, Canada, M5G 2M9 | |
Contact: Deborah Sanfelice, RN 416-946-4501 ext 2867 karen.yee@uhn.ca | |
Principal Investigator: Karen Yee, MD |
Study Director: | Stephen Anthony, DO | Tolero Pharmaceuticals |
Responsible Party: | Tolero Pharmaceuticals, Inc. |
ClinicalTrials.gov Identifier: | NCT02520011 History of Changes |
Other Study ID Numbers: |
TPI-ALV-201 |
First Posted: | August 11, 2015 Key Record Dates |
Last Update Posted: | January 16, 2018 |
Last Verified: | January 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
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 AML Newly diagnosed high-risk AML |
Additional relevant MeSH terms:
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms Cytarabine Alvocidib Mitoxantrone Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents |
Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Growth Inhibitors Growth Substances Protein Kinase Inhibitors |