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Trial record 1 of 1 for:    NCT02520011
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Alvocidib Biomarker-driven Phase 2 AML Study

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Tolero Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Tolero Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02520011
First received: August 6, 2015
Last updated: June 12, 2017
Last verified: February 2017
  Purpose
The purpose of this two-stage Phase 2 study is to assess the clinical response (Complete Remission) to FLAM compared to AM treatment in refractory or relapsed AML patients with demonstrated NOXA BH3 priming of ≥ 40% by mitochondrial profiling in bone marrow.

Condition Intervention Phase
Acute Myeloid Leukemia Drug: Alvocidib Drug: Cytarabine Drug: Mitoxantrone Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Tolero Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Complete Remission (CR) rate = Percentage of patients achieving CR [ Time Frame: 3 months ]

Secondary Outcome Measures:
  • 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 ]

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

Estimated Enrollment: 99
Actual Study Start Date: March 14, 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

Detailed Description:

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 exploratory arm, all eligible patients with newly diagnosed high-risk AML with NOXA BH3 priming ≥40% by mitochondrial profiling in bone marrow will receive treatment with ACM.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.
  4. Demonstrate NOXA BH3 priming 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 during and for 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02520011

Contacts
Contact: Susan C Smith, MSN 210-414-7702 su.smith@toleropharma.com

Locations
United States, Georgia
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Shondolyn Hilton Richburg    404-851-6707    Shondolyn.Hilton@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: Jackie Greer    410-614-1329    jgreer6@jhmi.edu   
Principal Investigator: B. Douglas Smith, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Sarah DeNobile    212-342-3884    sd2951@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         
United States, Texas
Baylor Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Grace Townsend    214-818-8382    grace.townsend@baylorhealth.edu   
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         
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         
Sponsors and Collaborators
Tolero Pharmaceuticals, Inc.
Investigators
Study Director: Robert Imani, MD, PhD Tolero Pharmaceuticals
  More Information

Responsible Party: Tolero Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02520011     History of Changes
Other Study ID Numbers: TPI-ALV-201
Study First Received: August 6, 2015
Last Updated: June 12, 2017
Individual Participant Data  
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

ClinicalTrials.gov processed this record on June 22, 2017