Alvocidib Biomarker-driven Phase 2 AML Study



Status:Recruiting
Conditions:Blood Cancer, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - 65
Updated:3/22/2019
Start Date:March 14, 2016
End Date:December 2020
Contact:Judy Costas, BSN
Email:jcostas@toleropharma.com
Phone:361-649-9176

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Phase 2, Randomized, Biomarker-driven Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With an Exploratory Arm in Patients With Newly Diagnosed High-Risk AML and Exploratory Arms With Varying Levels of MCL-1 Dependence

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.

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.

In the NDHR exploratory arm, all eligible patients with newly diagnosed high-risk (NDHR) AML
with MCL-1 dependence of ≥40% by mitochondrial profiling in bone marrow will receive
treatment with ACM.

In the MCL-1 dependency exploratory arms, all eligible AML patients with demonstrated MCL-1
dependence of ≥ 30 - <40% (Arm A), 15% - <30% (Arm B), or 0 - <15% (Arm C) by mitochondrial
profiling in bone marrow who are either in first relapse (within 24 months of CR) or have
primary refractory AML (ie, no CR or CRi after 2 cycles of intensive anthracycline/cytarabine
± etoposide or cladribine induction) will receive treatment with ACM.

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) or have newly diagnosed high-risk AML
as defined in this protocol.

*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, 30 -
<40% for MCL-1 Dependency Exploratory Arm A, 15% - <30% (MCL-1 Dependency Exploratory
Arm B), or 0 - <15% (MCL-1 Dependency Exploratory Arm C)

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

17. Have received any live vaccine within 14 days prior to first study drug
administration.
We found this trial at
22
sites
19 Bradhurst Avenue
Hawthorne, New York 10532
Principal Investigator: Karen Seiter, MD
Phone: 914-493-8375
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
Principal Investigator: Carlos Vigil, MD
Phone: 319-353-6347
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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Iowa City, IA
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1000 Johnson Ferry Rd NE
Atlanta, Georgia 30342
(404) 851-8000
Principal Investigator: Lawrence Morris, MD
Phone: 404-780-7965
Northside Hospital Northside Hospital-Atlanta (in Sandy Springs) opened in 1970. The original facility had 250...
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Baltimore, Maryland 21231
Principal Investigator: B. Douglas Smith, MD
Phone: 410-614-5407
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Baltimore, MD
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Elm St,
Buffalo, New York 14263
(716) 845-2300
Principal Investigator: Eunice Wang, MD
Phone: 716-845-1516
Roswell Park Cancer Center Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer...
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Buffalo, NY
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Chapel Hill, North Carolina 27599
(919) 962-2211
Principal Investigator: Joshua Zeidner, MD
Phone: 984-974-8251
Univ of North Carolina Carolina’s vibrant people and programs attest to the University’s long-standing place...
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Chapel Hill, NC
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2049 E 100th St
Cleveland, Ohio 44106
(216) 444-2200
Principal Investigator: Aziz Nazha, MD
Phone: 216-445-7009
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
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Cleveland, OH
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Dallas, Texas 75246
Principal Investigator: Moshe Levy, MD
Phone: 214-820-4266
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Durham, North Carolina 27710
Principal Investigator: David Rizzieri, MD
Phone: 919-681-4769
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1001 E 5th St
Greenville, North Carolina 27858
(252) 328-6131
Principal Investigator: Darla Liles, MD
Phone: 252-744-4924
East Carolina University Whether it's meeting the demand for more teachers and healthcare professionals or...
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Greenville, NC
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Houston, Texas 77030
Principal Investigator: Jorge Cortes, MD
Phone: 713-794-4460
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Houston, TX
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4500 San Pablo Rd S
Jacksonville, Florida 32224
(904) 953-2000
Principal Investigator: James Foran, MD
Phone: 855-776-0015
Mayo Clinic Florida Thousands of people come to Mayo Clinic in Jacksonville, Fla., annually for...
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Los Angeles, California 90095
Principal Investigator: Gary Schiller, MD
Phone: 310-794-0242
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8701 W Watertown Plank Rd
Milwaukee, Wisconsin
(414) 955-8296
Principal Investigator: Ehab Atallah, MD
Phone: 414-805-0596
Medical College of Wisconsin The Medical College (MCW) of Wisconsin is a major national research...
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New Orleans, Louisiana 70121
Principal Investigator: Andrew Dalovisio, MD
Phone: 504-842-0275
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New Orleans, LA
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630 W 168th St
New York, New York
212-305-2862
Principal Investigator: Daniel Lee, MD
Phone: 212-304-5585
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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Emile St
Omaha, Nebraska 68198
(402) 559-4000
Principal Investigator: Vijaya Bhatt, MD
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
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200 First Street SW
Rochester, Minnesota 55905
507-284-2511
Principal Investigator: Mark Litzow, MD
Phone: 855-776-0015
Mayo Clinic Rochester Mayo Clinic is a nonprofit worldwide leader in medical care, research and...
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San Diego, California 92103
Principal Investigator: Matthew Wieduwilt, MD, PhD
Phone: 858-822-5364
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10510 North 92nd Street
Scottsdale, Arizona 85251
Principal Investigator: Jeffrey Schriber, MD
Phone: 480-323-1973
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Toronto, Ontario
Principal Investigator: Karen Yee, MD
Phone: 416-946-4501
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Westwood, Kansas 66205
Principal Investigator: Tara Lin, MD
Phone: 913-945-7552
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