Trial Period
10/2018 - 03/2023
Conditions
Acute Myeloid Leukemia Relapsed or Refractory Acute Myeloid Leukemia Leukemia AML
(47) Trial Site Locations
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Clinical Trial AML003: Older Patients with Acute Myeloid Leukemia (AML) – Relapsed or Refractory

Trial ID: AML003 | NCT03504410

Phase III Multicenter Open-Label Randomized Trial to Evaluate Efficacy and Safety of CPI-613® (devimistat) in Combination with High Dose Cytarabine and Mitoxantrone (CHAM) Compared to High Dose Cytarabine and Mitoxantrone (HAM) therapy and control sub-groups: combination of Mitoxantrone, Etoposide and Cytarabine (MEC) and combination of Fludarabine, Cytarabine, and Filgrastim (FLAG) in Older Patients (≥ 50 years) with Relapsed/Refractory Acute Myeloid Leukemia (AML)

Trial Details

  • Gender(s)
  • 3 Phase
  • ≥50 Age Range
  • 47 Locations
  • Recruiting
Trial Period
10/2018 - 03/2023
Conditions
Acute Myeloid Leukemia Relapsed or Refractory Acute Myeloid Leukemia Leukemia AML
(47) Trial Site Locations
View on Map

For Patients

Get information about indications and participating in clinical trials that match your diagnoses.

More Info

For Physicians

Learn about treatments and read the latest news and resources for health professionals.

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Treatment Options

Study Arms Assigned Intervention
Arm 1: CPI-613®, High-Dose Cytarabine, Mitoxantrone Drugs: CPI-613®, Cytarabine, Mitoxantrone
Arm 2: Control- High-Dose Cytarabine, Mitoxantrone
  • Control sub-group 1: Mitoxantrone, Etoposide and Cytarabine (MEC)
  • Control sub-group 2: Fludarabine, Cytarabine, and Filgrastim (FLAG)

  • Drugs: Mitoxantrone, Etoposide and Cytarabine (MEC)
  • Drugs: Fludarabine, Cytarabine, and Filgrastim (FLAG)

Trial Site Locations (47)

View All Locations
University of Chicago Medical Center 5841 S. Maryland Ave
MC-2115
Chicago, IL 60637
USA
Contact Info: Calvin Pullins 773-702-7871 cpullins1@medicine.bsd.uchicago.edu
Oregon Health & Science University 3485 SW Bond Avenue
Portland, OR 97239
USA
Contact Info: Tara Lundberg Williams 503-346-0010 lundbert@ohsu.edu
University of Texas Southwestern Medical Center 2201 Inwood Rd
Dallas, TX 75390
USA
Contact Info: Jessica Henderson 214-648-1183 jessica.henderson@UTSouthwestern.edu
University of Cincinnati Medical Center – Hoxworth Center 3130 Highland Ave
Cincinnati, OH 45219
USA
Contact Info: Maria P Quintas 513-584-0222 pascuama@ucmail.uc.edu
UC Irvine Health Chao Family Comprehensive Cancer Center 101 The City Drive
South Orange, CA 92868
USA
Contact Info: An To 714-509-2369 Aqto@uci.edu
University of Virginia Health System Cancer Center 1300 Jefferson Park Ave
Charlottesville, VA 22908
USA
Contact Info: Megan Healy 434-297-7783 mkh6b@virginia.edu
Stony Brook University Hospital – Stony Brook University Medical Center 3 Edmund D Pellegrino Rd
Stony Brook, NY 11794
USA
Contact Info: Sebastian Munoz sebastian.munoz@stonybrookmedicine.edu
Baylor Scott & White Medical Center Temple 2401 South 31st St
Temple, TX 76508
USA
Contact Info: Theresa Strakos 254-724-1291 Theresa.Strakos@BSWHealth.org
University of Iowa Hospitals & Clinics 200 Hawkins Dr
Iowa City, IA 52242
USA
Contact Info: Karen Parrott 319-353-6347 karen-parrott@uiowa.edu
Atlantic Health System Cancer Care 100 Madison Avenue Morristown
Morristown, NJ 07960
USA
Contact Info: Christie Rice 973-971-5235 christie.rice@atlantichealth.org
Wake Forest University Health Sciences Section on Hem & Onc
Winston-Salem, NC 27157
USA
Contact Info: Tong Chen 336-444-7923 tchen@wakehealth.edu
Cleveland Clinic 9500 Euclid Ave
Cleveland, OH 44195
USA
Contact Info: Aziz Nazha
Seoul National University Hospital 101 Daehak-Ro, Jongno-Gu
Seoul,
South Korea
Contact Info: KyungWha Choo 82-2-6072-5179 gigs407@naver.com
Centre Hospitalier de Versailles – Hôpital André Mignot Service Hématologie et Oncologie
Le Chesnay, 78157
France
Contact Info: Anais Beulaygue 331 392 39773 abeulaygue@ch-versailles.fr
Texas Oncology – Baylor Charles A. Sammons Cancer Center 3410 Worth Street
Suite 560
Dalls, TX 75246
USA
Severance Hospital 50-1, Yonsei-ro
Seoul 03722
South Korea
Contact Info: Sohyun Jun
CHU la Conecption 147 Boulevard Baille
Marseille Cedex 05, 13385
France
Contact Info: Mauine Duhayon
Hanuschkrankenhaus der WGKK Hanuschkrankenhaus der WGKK
Vienna, 1140
Austria
Contact Info: Kathrin Holzer
Algemeen Ziekenhuis Sint-Jan Ruddershove 10
Brugge, Belgium 8000
Contact Info: Thomas DeFauw 032 (0)50 45 30 62 Thomas.DeFauw@azsintjan.be
Clinique Universitaire St Luc Avenue Hippocrate 10
Brussel, 1200
Belgium
University of Kentucky Medical Center 800 Rose St, CC447
Lexington, KY 40536
USA
Contact Info: Corisa Logan 859-323-5785 corisa.logan@uky.edu
HonorHealth Research Institute 9003 E Shea Blvd.
Scottsdale, Arizona 85260
USA
Contact Info: Mei Yu / Nyssa Hoffman 480-882-5021 myu@honorhealth.com /nhoffman@honorhealth.com
Hospital Universitario Virgen de la Victoria Campus De Teatinos S/N
Malaga, 29071
Spain
Contact Info: Carolina Buendia +34 618302536 carollhamlet@hotmail.com
Rutgers Cancer Institute of NJ 195 Little Albany Street,
New Brunswick, NJ 08903
USA
Contact Info: Damayanti Bhavsar 732-235-4037 Bhavsadm@cinj.rutgers.edu

Key Eligibility Criteria

Inclusion Criteria
  1. Patient has provided an informed consent prior to initiation of any study specific activities/procedures
  2. Males and females age ≥ 50 years must have histologically documented AML that is relapsed from, or refractory to, prior standard therapies
  3. Refractory is defined as failure to achieve CR or CRi following:
    1. At least one cycle of any anthracycline, cytarabine or fludarabine containing induction regimen or persistence of disease on a nadir marrow following at least one cycle of any anthracycline, cytarabine or fludarabine containing induction regimen
    2. Persistent disease after at least 2 cycles of a hypomethylating agent (azacytidine or decitabine) with or without venetoclax
  4. Relapse is defined as development of recurrent AML (as described by Döhner et al, 2017)6
    after CR or CRi has been achieved with a prior chemotherapy or after disease progression ona hypomethylating agent with or without venetoclax.
  5. ECOG PS 0-2
  6. Expected survival greater than 3 months.
  7. Women of child-bearing potential (i.e. women who are pre-menopausal or < 2 years post-menopausal or not surgically sterile) must practice a highly effective method of birth control consistent with local regulations regarding the use of birth control methods. Examples: use of oral, injected or implanted hormonal methods of contraception; placement of an intra uterine device (IUD) or intrauterine system (IUS); male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence during and for 6 months after the last administered dose of CHAM or HAM therapy and control sub-groups (MEC and FLAG), and must have a negative serum pregnancy test within 1 week prior to treatment initiation and at 1st day of each cycle and at the end of systemic exposure. (Note: pregnant patients are excluded because the effects of CPI-613® (devimistat) on a fetus are unknown)
  8. Fertile men who are sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository during the study period and up to 6 months after completion of the study screening, unless documentation of infertility exists
  9. Good state of mental health, ability to understand and willingness to sign the informed consent form (ICF).
  10. No radiotherapy, treatment with cytotoxic chemotherapy, treatment with biologic agents or any anti-cancer therapy for R/R AML within the 1 week prior to treatment with CPI-613® (devimistat). Hydroxyurea and/or venetoclax and oral tyrosine kinase (FLT3) or Isocitrate Dehydrogenase 1 and 2 (IDH1/2), BCL-2 or hedgehog inhibitors being used with Grade ≤ 2 toxicity can be taken until the day prior to starting of CHAM or HAM therapy or control sub-groups (MEC and FLAG). Previous exposure to a hypomethylating agent either alone or in combination with Isocitrate Dehydrogenase 1 and 2 (IDH1/2), BCL-2 or hedgehog inhibitors are allowed until the day prior to starting of CHAM or HAM therapy and control sub-groups (MEC and FLAG). Patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities with the exception of alopecia (returned to baseline status as noted before most recent treatment). Patients with persisting, non-hematologic, non-infectious toxicities from prior treatment Grade ≤ 2 are eligible but must be documented as such
  11. Laboratory values ≤ 2 weeks before dosing must be:
    1. Adequate hepatic function (aspartate aminotransferase/serum glutamic-oxaloacetic transaminase [AST/SGOT] ≤ 5 x upper limit of normal [ULN], alanine aminotransferase/serum glutamic oxaloacetic transaminase [ALT/SGPT] ≤ 5 × ULN, bilirubin ≤ 1.5 × ULN)
    2. Adequate renal function (serum creatinine clearance ≥ 60 mL/min per CockCroft-Gault formula)
    3. Adequate coagulation (International Normalized Ratio [INR] must be < 1.7 unless on vitamin k antagonist anticoagulation)
  12. Left Ventricular Ejection Fraction (LVEF) by Transthoracic Echocardiogram (TTE) or Multigated Acquisition Scan (MUGA) or cardiac Magnetic Resonance Imaging (MRI), sufficient to safely administer mitoxantrone. Subjects must have an LVEF ≥ 45%
  13. No marked baseline prolongation of QT/QTc interval (repeated exhibition of a QTc interval > 480 ms for both male and female patients)
  14. No history of additional risk factors for torsade de pointes (e.g. clinically significant heart failure, hypokalemia, immediate family history of Long QT Syndrome)
  15. Allow only patients who experienced relapse after 1 year from previous HiDAC treatment or who didn’t receive HiDAC previously (Note: This inclusion applies only to South Korea)
Exclusion Criteria
  1. Patients who have received cytotoxic chemotherapy treatment for their current relapsed or refractory AML. (Treatment with hypomethylating agents (decitabine or azacytidine) either alone or in combination with venetoclax are allowed until the day prior to starting of CHAM or HAM therapy and control sub-groups (MEC and FLAG). Targeted therapies including FLT3 or IDH1/2 inhibitors and/or Hydrea and/or venetoclax are allowed. Targeted therapies and Hydrea may be taken until the day prior to starting CHAM or HAM therapy or control sub-groups (MEC and FLAG)
  2. Vulnerable adult and patient whose health conditions does not allow them to give their consent
  3. Vulnerable adult and patient whose health conditions does not allow them to give their consent
  4. History or evidence of any other clinically significant disorder, condition or disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic myocardial infection, uncontrolled cardiac arrhythmia, pericardial disease or heart failure New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients’ risk for toxicity and in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion
  5. Patients with active Central Nervous System (CNS) involvement (leukemic infiltration, blast in the spinal fluid)
  6. Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g. active peptic ulcer disease)
  7. Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of CHAM or HAM therapy or control sub-groups, MEC and FLAG (the teratogenic potential of CPI-613® (devimistat) is unknown). Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at Screening
  8. Women of childbearing potential (i.e. women who are pre-menopausal or < 2 years postmenopausal or not surgically sterile) unwilling to practice a highly effective method of birth control consistent with local regulations regarding the use of birth control methods during treatment and for 6 months after completion of CHAM or HAM therapy or control sub-groups, MEC and FLAG for AML
  9. Male patients with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 6 months after completion of CHAM or HAM therapy or control sub-groups, MEC and FLAG
  10. Male patients unwilling to abstain from donating sperm during treatment and for 6 months after completion of CHAM or HAM therapy or control sub-groups, MEC and FLAG with potential highest teratogenic risk
  11. Known hypersensitivity to study treatment drugs or any of the excipient(s) contained in the drug formulation
  12. Life expectancy less than 3 months
  13. Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
  14. Unwilling or unable to follow protocol requirements
  15. Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly)
  16. Patients with any amount of clinically significant pericardial effusion that requires drainage.
  17. Evidence of ongoing, uncontrolled bacterial, viral or fungal infection
  18. Patients with known human immunodeficiency virus infection
  19. History of other malignancy within the past 5 years, with the following exception(s):
    1. Malignancy treated with curative intent and with no known active disease present for ≥ 5 years before enrolment and felt to be at low risk for recurrence by the treating physician
    2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of recurrent or residual disease
    3. Adequately treated cervical carcinoma in situ without evidence of disease
    4. Prostate cancer Stage 1
  20. Patients receiving any other standard or investigational treatment for AML, or any other investigational agent for any indication within the past 1 week prior to initiation of CPI-613® (devimistat) treatment (the use of Hydrea and/or venetoclax, oral tyrosine kinase inhibitors FLT3 or IDH 1/2 inhibitors are allowed until the day prior to starting CHAM or HAM therapy or control sub-groups, MEC and FLAG. Previous exposure to a hypomethylating agent either alone or in combination with venetoclax are allowed until the day prior to starting of CHAM or HAM therapy and control sub-groups (MEC and FLAG))
  21. Patients who have received immunotherapy of any type within the past 1 week prior to initiation of CPI-613® (devimistat) treatment
  22. Requirement for immediate palliative treatment of any kind including minor surgery
  23. Patients who have received a chemotherapy regimen with autologous stem cell support (bone marrow transplantation) within 6 months of starting CHAM or HAM therapy or control sub-groups (MEC and FLAG)
  24. Patients who have had allogenic bone marrow transplantation within the last 6 months. Patients who have had an allogenic transplant more than 6 months ago are eligible provided they have no graft vs host disease. (Note: Exclude only patients with active GVHD requiring therapy with immunosuppressive agents and not patients with stable GVHD not requiring immunosuppression.)
  25. Cytarabine contraindications
    1. Hypersensitivity to the cytarabine or to any of the excipients of cytarabine injection.
    2. Anemia, leucopenia and thrombocytopenia of non-malignant aetiology (e.g bone marrow aplasia); unless the clinician feels that such management offers the most hopeful alternative for the patient.
    3. Degenerative and toxic encephalopathies, especially after the use of methotrexate or
      treatment with ionizing radiation
  26. Mitoxantrone contraindications
    1. Mitoxantrone Sterile Concentrate is contraindicated in patients who have demonstrated prior hypersensitivity to mitoxantrone hydrochloride, other anthracyclines or any of its components. Use in patients with profound bone marrow suppression is a relative contraindication depending on the clinical circumstances
    2. Mitoxantrone Sterile Concentrate should not be used during pregnancy or lactation
  27. Strong CYP450 inducers should be prohibited
  28. Fludarabine contraindications
    1. Contraindicated in those patients who are hypersensitive to this drug or its components
  29. Filgrastim contraindications
    1. Contraindicated in patients with known hypersensitivity to E coli-derived proteins‚ Filgrastim‚ or any component of the product

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