Relapsed/Refractory Acute Myeloid LeukemiaPhase 3NCT03504410
Efficacy/Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. in Older Patients With R/R AML
A Phase 3 study testing CPI-613 + High Dose Cytarabine and Mitoxantrone, High Dose Cytarabine and Mitoxantrone and Mitoxantrone, Etoposide and Cytarabine in people with Relapsed/Refractory Acute Myeloid Leukemia, run by Cornerstone Pharmaceuticals at 60 sites in 9 countries.
Trial summary
A Phase III study to evaluate the safety and efficacy of CPI-613® (devimistat) in combination with High Dose Cytarabine and Mitoxantrone in comparison with high dose Cytarabine and Mitoxantrone and control sub-groups: combination of Mitoxantrone, Etoposide and Cytarabine (MEC) and combination of Fludarabine… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Relapsed/Refractory Acute Myeloid Leukemia
- What is being tested?
- CPI-613 + High Dose Cytarabine and Mitoxantrone, High Dose Cytarabine and Mitoxantrone and Mitoxantrone, Etoposide and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 60 sitesin 9 countries
- Study dates
- 12 Nov 2018to 19 Jan 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has provided an informed consent prior to initiation of any study specific activities/procedures
- Males and females age ≥ 50 years must have histologically documented AML that is relapsed from, or refractory to, prior standard therapies
- Refractory is defined as failure to achieve CR or CRi following:
- 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
- Persistent disease after at least 2 cycles of a hypomethylating agent (azacytidine or decitabine) with or without venetoclax
- 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 on a hypomethylating agent with or without venetoclax
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- ECOG PS 0-2
- Expected survival greater than 3 months
- 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)
- 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
- Good state of mental health, ability to understand and willingness to sign the informed consent form (ICF)
- 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
- Laboratory values ≤ 2 weeks before dosing must be:
- 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)
- Adequate renal function (serum creatinine clearance ≥ 60 mL/min per CockCroft Gault formula)
- Adequate coagulation (International Normalized Ratio [INR] must be < 1.7 unless on vitamin k antagonist anticoagulation)
- 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%
- No marked baseline prolongation of QT/QTc interval (repeated exhibition of a QTc interval > 480 ms for both male and female patients)
- No history of additional risk factors for torsade de pointes (e.g. clinically significant heart failure, hypokalemia, immediate family history of Long QT Syndrome)
- 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)
Who cannot join
- 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)
- Vulnerable adult and patient whose health conditions does not allow them to give their consent
- 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
- Patients with active Central Nervous System (CNS) involvement (leukemic infiltration, blast in the spinal fluid)
- Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g. active peptic ulcer disease)
- 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
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- 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
- 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
- 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
- Known hypersensitivity to study treatment drugs or any of the excipient(s) contained in the drug formulation
- Life expectancy less than 3 months
- Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
- Unwilling or unable to follow protocol requirements
- Patients with large and recurrent pleural or peritoneal effusions requiring frequent drainage (e.g. weekly)
- Patients with any amount of clinically significant pericardial effusion that requires drainage.
- Evidence of ongoing, uncontrolled bacterial, viral or fungal infection
- Patients with known human immunodeficiency virus infection
- History of other malignancy within the past 5 years, with the following exception(s):
- 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
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of recurrent or residual disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostate cancer Stage 1
- 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))
- Patients who have received immunotherapy of any type within the past 1 week prior to initiation of CPI-613® (devimistat) treatment
- Requirement for immediate palliative treatment of any kind including minor surgery
- 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)
- 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.)
- Cytarabine contraindications
- Hypersensitivity to the cytarabine or to any of the excipients of cytarabine injection
- 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
- Degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation
- Mitoxantrone contraindications
- 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
- Mitoxantrone Sterile Concentrate should not be used during pregnancy or lactation
- Strong CYP450 inducers should be prohibited
- Etoposide contraindications
- •. Contraindicated in patients with a history of a severe hypersensitivity reaction to etoposide products
- Fludarabine contraindications
- •. Contraindicated in those patients who are hypersensitive to this drug or its components
- Filgrastim contraindications •. Contraindicated in patients with known hypersensitivity to E coli-derived proteins, Filgrastim, or any component of the product
Trial locations and contacts
60 sites in 9 countries.
60 sites in 9 countries
United States23 sites
UNC Chapel Hill
Chapel Hill, North Carolina, 27599
University of Virginia
Charlottesville, Virginia, 22908
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Chicago
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45219
Cleveland Clinic
Cleveland, Ohio, 44195
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
University of Texas - Southwestern Medical Center
Dallas, Texas, 75390
MD Andrson Cancer Center
Houston, Texas, 77030
University of Iowa-Holden Cancer Care Center
Iowa City, Iowa, 52242
University of Kentucky
Lexington, Kentucky, 40436
Stony Brook University Hospital
Long Island City, New York, 11794
Norton Cancer Institute
Louisville, Kentucky, 40207
Loyola University Medical Center
Maywood, Illinois, 60153
Atlantic Health System
Morristown, New Jersey, 07960
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Chao Family Comprehensive Cancer Center (University of California Irvine)
Orange, California, 92868
Oregon Health & Science University
Portland, Oregon, 97239
California Pacific Medical Center
San Francisco, California, 94115
Honor Health Research Institute
Scottsdale, Arizona, 85258
Baylor Temple (BSW)
Temple, Texas, 76508
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
France9 sites
CHU Amiens
Amiens, 80054
Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris
Bobigny, 9300
CHU de Caen
Caen, 14033
Centre Hospitalier Universitaire Grenoble Hopital Michalon
Grenoble, 38043
Centre Hospitalier de Versailles - Hôpital André Mignot
Le Chesnay, Yvelines, 78157
CHU la Conecption
Marseille, 13005
CHU de Nice
Nice, 06202
Hopital Saint Louis
Paris, 75010
Centre hospitalier Lyon Sud
Pierre-Bénite, 69495
Spain7 sites
Institut Catala d'Oncologia (ICO) - Hospital Universitari Germans Trias i Pujol
Badalona, 08916
Hospital Vall d'Hebron
Barcelona, 08035
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario Virgen de la Victoria
Málaga, 29010
Hospital Son ESPASES
Palma de Mallorca, 07120
Hospital Clínico Universitario de Salamanca
Salamanca, 37007
Hospital U. P. La Fe
Valencia, 46026
Australia4 sites
Border Medical Oncology Research Unit
Albury, New South Wales, 2640
Gosford Hospital
Gosford, New South Wales, 2250
Royal Perth Hospital
Perth, Western Australia, 6000
Calvary Mater Newcastle Hospital
Waratah, New South Wales, 2298
Germany4 sites
Klinikum Frankfurt Hoechst
Frankfurt, 65929
UniversitatsklinikumUKSH Kiel
Kiel, 24105
Universitatsklinikum Marburg
Marburg, 35033
Robert-Bosch- Krankenhaus
Stuttgart, 70376
South Korea4 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital
Seoul, 03722
Asan Medical Center
Seoul, 05505
Samsung Medical Center
Seoul, 06351
Austria3 sites
Universitätsklinik für Innere Medizin
Graz, 8036
Paracelsus Medical University
Salzburg, 5020
Hanuschkrankenhaus der WGKK
Vienna, 1140
Belgium3 sites
Algemeen Ziekenhuis Sint-Jan
Bruges, 8000
Clinique Universitaire St Luc
Brussels, 1200
UN Gent
Ghent, 9000
Poland3 sites
Zespół Szpitali Miejskich w Chorzowie
Chorzów, 41500
Uniwersyteckie Centrum Kliniczne Klinika Hematologii i Transplantologii
Gdansk, 80211
Katedra i Klinika Hematologii
Wroclaw, 50556
About this study
Official title: Phase 3 Multicenter Randomized Trial to Evaluate Efficacy and Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. Therapy and Control Sub-groups in Older Patients With R/R AML
A Phase III study to evaluate the safety and efficacy of CPI-613® (devimistat) in combination with High Dose Cytarabine and Mitoxantrone in comparison with high dose Cytarabine and Mitoxantrone and control sub-groups: combination of Mitoxantrone, Etoposide and Cytarabine (MEC) and combination of Fludarabine, Cytarabine, and Filgrastim (FLAG) in older patients with relapsed/refractory Acute Myeloid Leukemia. CPI-613® (devimistat) targets the altered energy metabolism and processes for production of ATP and essential bio-intermediates unique to and characteristic of most cancer cell types. The addition of CPI-613® (devimistat) to high dose cytarabine and mitoxantrone (CHAM) will improve the complete remission (CR) rate in patients 50 years or older with relapsed or refractory AML when compared to HAM alone or other control sub groups.
Read the detailed description
Subjects were randomized in 1:1 allocation ratio by IWRS according to the stratification factors. However, the control sub-groups (MEC and FLAG) were capped at 100 (50 per sub-group).
Subjects in both Arm 1 and Arm 2 were planned to receive induction cycle 1 treatment for at least 14 days. Subjects will receive follow-up therapy based on results of the bone marrow aspirate, and CR/complete remission with incomplete recovery (CRi) status.
- Being tested
- CPI-613 + High Dose Cytarabine and Mitoxantrone, High Dose Cytarabine and Mitoxantrone, Mitoxantrone, Etoposide and Cytarabine, Fludarabine, Cytarabine, Filgrastim
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CPI-613 + High Dose Cytarabine and MitoxantroneDrug
Also called CPI-613, CHAM
CPI-613 + High Dose Cytarabine and Mitoxantrone CPI-613: 2000mg/m2, 5 doses once a day, days 1-5 Cytarabine 1gm/m2, 5 doses every 12hrs starting day 3 through day 5 Mitoxantrone 6mg/m2, 3 doses, once a day following the first, third and fifth doses of Cytarabine
High Dose Cytarabine and MitoxantroneDrug
Also called HAM
Cytarabine 1gm/m2, 5 doses every 12hrs starting day 3 through day 5 Mitoxantrone 6mg/m2, 3 doses, once a day following the first, third and fifth doses of Cytarabine
Mitoxantrone, Etoposide and CytarabineDrug
Also called MEC
Mitoxantrone, Etoposide and Cytarabine
Etoposide 80mg/m over 60 minutes as a central line IV infusion; 6 doses Day 1 though 6 Cytarabine 1000mg/m2 over 3 hours as a central line IV infusion: 6 doses, Day 1 through 6 Mitoxantrone 6 mg/m2 over 30 minutes as a central line IV infusion: 6 dose, Day 1 through 6
Fludarabine, Cytarabine, FilgrastimDrug
Also called FLAG
Fludarabine, Cytarabine and Filgrastim
Fludarabine 30mg/m2/day over 30 minutes as a central line IV infusion; 5 doses Day 1 though 5 Cytarabine 2g/m2 over 4 hours as a central line IV infusion: 4 hours after Fludarabine: 5 doses, Day 1 through 5 Filgrastim 5µg/kg/day by SQ or as per institutional guidelines starting from Day 1 through Day 5
| Study group | Role | What they receive |
|---|---|---|
| CPI-613 + HD Cytarabine and Mitoxantrone | Experimental | CPI-613 + High Dose Cytarabine and Mitoxantrone
CPI-613 at 2,000 mg/m2/day from day 1 to 5.
Cytarabine at 1gm/m2 (5 doses), every 12 hours starting day 3. Mitoxantrone at 6gm/m2 (3 doses), everyday following the 1st, 2nd and 5th doses of Cytarabine. Receives: Drug: CPI-613 + High Dose Cytarabine and Mitoxantrone |
| Control (HAM) and control sub-groups (MEC and FLAG) | Active comparator | High Dose Cytarabine and Mitoxantrone
Cytarabine at 1gm/m2 (5 doses), every 12 hours starting day 3. Mitoxantrone at 6gm/m2 (3 doses), everyday following the 1st, 3rd and 5th doses of Cytarabine.
Mitoxantrone, Etoposide and Cytarabine
Etoposide 80mg/m over 60 minutes as a central line IV infusion; 6 doses Day 1 though 6 Cytarabine 1000mg/m2 over 3 hours as a central line IV infusion: 6 doses, Day 1 through 6 Mitoxantrone 6 mg/m2 over 30 minutes as a central line IV infusion: 6 dose, Day 1 through 6
Fludarabine, Cytarabine and Filgrastim
Fludarabine 30mg/m2/day over 30 minutes as a central line IV infusion; 5 doses Day 1 though 5 Cytarabine 2g/m2 over 4 hours as a central line IV infusion: 4 hours after Fludarabine: 5 doses, Day 1 through 5 Filgrastim 5µg/kg/day by SQ or as per institutional guidelines starting from Day 1 through Day 5 Receives: Drug: High Dose Cytarabine and Mitoxantrone; Drug: Mitoxantrone, Etoposide and Cytarabine; Drug: Fludarabine, Cytarabine, Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR)
Complete disappearance of all clinical evidence of disease
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2018
- Study start12 Nov 2018
- Primary completion25 Oct 2021
- Study completion19 Jan 2022
Why it stopped: Futile
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed/Refractory Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cornerstone Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jorge E Cortes, MD, Principal investigator, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03504410
- Sponsor's protocol ID
- AML003
- Status last verified
- Jan 2023
- First submitted
- 12 Apr 2018
- Last updated
- 8 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pardee TS, Powell BL, Larson RA, Maly J, Keng M, Foster M, Choi EJ, Sill H, Cluzeau T, Jeyakumar D, Frankfurt O, Patel P, Schuster M, Koller E, Costello R, Platzbecker U, Montesinos P, Vives S, Nazha A, Cook R, Vigil-Gonzales C, Chantepie S, Luther S, Cortes J. Devimistat plus chemotherapy vs chemotherapy alone for older relapsed or refractory patients with AML: results of the ARMADA trial. Blood Neoplasia. 2024 Mar 29;1(2):100009. doi: 10.1016/j.bneo.2024.100009. eCollection 2024 Jun.
PubMed 40454396
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Multicenter Randomized Trial to Evaluate Efficacy and Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. Therapy and Control Sub-groups in Older Patients With R/R AML
- ClinicalTrials.gov ID
- NCT03504410
- Acronym / sponsor ID
- AML003
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futile
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Cornerstone PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- 25 Oct 2021 (actual)
- Study completion
- 19 Jan 2022 (actual)
- First posted
- 20 Apr 2018 (actual)
- Results
- Posted 13 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase III study to evaluate the safety and efficacy of CPI-613® (devimistat) in combination with High Dose Cytarabine and Mitoxantrone in comparison with high dose Cytarabine and Mitoxantrone and control sub-groups: combination of Mitoxantrone, Etoposide and Cytarabine (MEC) and combination of Fludarabine, Cytarabine, and Filgrastim (FLAG) in older patients with relapsed/refractory Acute Myeloid Leukemia. CPI-613® (devimistat) targets the altered energy metabolism and processes for production of ATP and essential bio-intermediates unique to and characteristic of most cancer cell types. The addition of CPI-613® (devimistat) to high dose cytarabine and mitoxantrone (CHAM) will improve the complete remission (CR) rate in patients 50 years or older with relapsed or refractory AML when compared to HAM alone or other control sub groups.
Detailed description
Subjects were randomized in 1:1 allocation ratio by IWRS according to the stratification factors. However, the control sub-groups (MEC and FLAG) were capped at 100 (50 per sub-group).
Subjects in both Arm 1 and Arm 2 were planned to receive induction cycle 1 treatment for at least 14 days. Subjects will receive follow-up therapy based on results of the bone marrow aspirate, and CR/complete remission with incomplete recovery (CRi) status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPI-613 + HD Cytarabine and Mitoxantrone | Experimental | Drug: CPI-613 + High Dose Cytarabine and MitoxantroneCPI-613 + High Dose Cytarabine and Mitoxantrone CPI-613 at 2,000 mg/m2/day from day 1 to 5. Cytarabine at 1gm/m2 (5 doses), every 12 hours starting day 3. Mitoxantrone at 6gm/m2 (3 doses), everyday following the 1st, 2nd and 5th doses of Cytarabine. |
| Control (HAM) and control sub-groups (MEC and FLAG) | Active comparator | Drug: High Dose Cytarabine and Mitoxantrone, Drug: Mitoxantrone, Etoposide and Cytarabine, Drug: Fludarabine, Cytarabine, FilgrastimHigh Dose Cytarabine and Mitoxantrone Cytarabine at 1gm/m2 (5 doses), every 12 hours starting day 3. Mitoxantrone at 6gm/m2 (3 doses), everyday following the 1st, 3rd and 5th doses of Cytarabine. Mitoxantrone, Etoposide and Cytarabine Etoposide 80mg/m over 60 minutes as a central line IV infusion; 6 doses Day 1 though 6 Cytarabine 1000mg/m2 over 3 hours as a central line IV infusion: 6 doses, Day 1 through 6 Mitoxantrone 6 mg/m2 over 30 minutes as a central line IV infusion: 6 dose, Day 1 through 6 Fludarabine, Cytarabine and Filgrastim Fludarabine 30mg/m2/day over 30 minutes as a central line IV infusion; 5 doses Day 1 though 5 Cytarabine 2g/m2 over 4 hours as a central line IV infusion: 4 hours after Fludarabine: 5 doses, Day 1 through 5 Filgrastim 5µg/kg/day by SQ or as per institutional guidelines starting from Day 1 through Day 5 |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patient has provided an informed consent prior to initiation of any study specific activities/procedures
- Males and females age ≥ 50 years must have histologically documented AML that is relapsed from, or refractory to, prior standard therapies
- Refractory is defined as failure to achieve CR or CRi following:
- 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 on a hypomethylating agent with or without venetoclax
- ECOG PS 0-2
Key exclusion criteria (40 listed)
- 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)
- Vulnerable adult and patient whose health conditions does not allow them to give their consent
- 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
- Patients with active Central Nervous System (CNS) involvement (leukemic infiltration, blast in the spinal fluid)
- Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g. active peptic ulcer disease)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CPI-613 + High Dose Cytarabine and MitoxantroneAlso: CPI-613, CHAMCPI-613 + High Dose Cytarabine and Mitoxantrone CPI-613: 2000mg/m2, 5 doses once a day, days 1-5 Cytarabine 1gm/m2, 5 doses every 12hrs starting day 3 through day 5 Mitoxantrone 6mg/m2, 3 doses, once a day following the first, third and fifth doses of Cytarabine | Drug | CPI-613 + HD Cytarabine and Mitoxantrone |
| High Dose Cytarabine and MitoxantroneAlso: HAMCytarabine 1gm/m2, 5 doses every 12hrs starting day 3 through day 5 Mitoxantrone 6mg/m2, 3 doses, once a day following the first, third and fifth doses of Cytarabine | Drug | Control (HAM) and control sub-groups (MEC and FLAG) |
| Mitoxantrone, Etoposide and CytarabineAlso: MECMitoxantrone, Etoposide and Cytarabine Etoposide 80mg/m over 60 minutes as a central line IV infusion; 6 doses Day 1 though 6 Cytarabine 1000mg/m2 over 3 hours as a central line IV infusion: 6 doses, Day 1 through 6 Mitoxantrone 6 mg/m2 over 30 minutes as a central line IV infusion: 6 dose, Day 1 through 6 | Drug | Control (HAM) and control sub-groups (MEC and FLAG) |
| Fludarabine, Cytarabine, FilgrastimAlso: FLAGFludarabine, Cytarabine and Filgrastim Fludarabine 30mg/m2/day over 30 minutes as a central line IV infusion; 5 doses Day 1 though 5 Cytarabine 2g/m2 over 4 hours as a central line IV infusion: 4 hours after Fludarabine: 5 doses, Day 1 through 5 Filgrastim 5µg/kg/day by SQ or as per institutional guidelines starting from Day 1 through Day 5 | Drug | Control (HAM) and control sub-groups (MEC and FLAG) |
Primary outcome
Complete Remission (CR)
Time frame: 12 months
Complete disappearance of all clinical evidence of disease
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40454396Pardee TS, Powell BL, Larson RA, Maly J, Keng M, Foster M, Choi EJ, Sill H, Cluzeau T, Jeyakumar D, Frankfurt O, Patel P, Schuster M, Koller E, Costello R, Platzbecker U, Montesinos P, Vives S, Nazha A, Cook R, Vigil-Gonzales C, Chantepie S, Luther S, Cortes J. Devimistat plus chemotherapy vs chemotherapy alone for older relapsed or refractory patients with AML: results of the ARMADA trial. Blood Neoplasia. 2024 Mar 29;1(2):100009. doi: 10.1016/j.bneo.2024.100009. eCollection 2024 Jun.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge E Cortes, MD principal investigator
Augusta University
60 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CPI-613 + High Dose Cytarabine and Mitoxantrone, High Dose Cytarabine and Mitoxantrone and Mitoxantrone, Etoposide and Cytarabine in people with Relapsed/Refractory Acute Myeloid Leukemia, run by Cornerstone Pharmaceuticals at 60 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 60 sites in United States, France, Spain, Australia, Germany and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission (CR) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03504410, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.