Acute Myeloid Leukemia Clinical Trial

Efficacy/Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. in Older Patients With R/R AML

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, 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.

View Full Description

Full 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.

View Eligibility Criteria

Eligibility Criteria

INCLUSION CRITERIA:

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
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)

EXCLUSION CRITERIA:

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
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

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 3

Estimated Enrollment:

200

Study ID:

NCT03504410

Recruitment Status:

Terminated

Sponsor:

Cornerstone Pharmaceuticals

Check Your Eligibility

Let’s see if you might be eligible for this study.

What is your age and gender ?

Submit

There are 60 Locations for this study

See Locations Near You

Honor Health Research Institute
Scottsdale Arizona, 85258, United States
Chao Family Comprehensive Cancer Center (University of California Irvine)
Orange California, 92868, United States
California Pacific Medical Center
San Francisco California, 94115, United States
Northwestern Memorial Hospital
Chicago Illinois, 60611, United States
University of Chicago
Chicago Illinois, 60637, United States
Loyola University Medical Center
Maywood Illinois, 60153, United States
University of Iowa-Holden Cancer Care Center
Iowa City Iowa, 52242, United States
University of Kentucky
Lexington Kentucky, 40436, United States
Norton Cancer Institute
Louisville Kentucky, 40207, United States
Atlantic Health System
Morristown New Jersey, 07960, United States
Rutgers Cancer Institute of New Jersey
New Brunswick New Jersey, 08901, United States
Stony Brook University Hospital
Long Island City New York, 11794, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
UNC Chapel Hill
Chapel Hill North Carolina, 27599, United States
Wake Forest Baptist Health
Winston-Salem North Carolina, 27157, United States
University of Cincinnati
Cincinnati Ohio, 45219, United States
Cleveland Clinic
Cleveland Ohio, 44195, United States
Oregon Health & Science University
Portland Oregon, 97239, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas Texas, 75246, United States
University of Texas - Southwestern Medical Center
Dallas Texas, 75390, United States
MD Andrson Cancer Center
Houston Texas, 77030, United States
Baylor Temple (BSW)
Temple Texas, 76508, United States
University of Virginia
Charlottesville Virginia, 22908, United States
Border Medical Oncology Research Unit
Albury New South Wales, 2640, Australia
Gosford Hospital
Gosford New South Wales, 2250, Australia
Calvary Mater Newcastle Hospital
Waratah New South Wales, 2298, Australia
Royal Perth Hospital
Perth Western Australia, 6000, Australia
Universitätsklinik für Innere Medizin
Graz , 8036, Austria
Paracelsus Medical University
Salzburg , 5020, Austria
Hanuschkrankenhaus der WGKK
Wien , 1140, Austria
Algemeen Ziekenhuis Sint-Jan
Brugge , 8000, Belgium
Clinique Universitaire St Luc
Brussels , 1200, Belgium
UN Gent
Gent , 9000, Belgium
Centre Hospitalier de Versailles - Hôpital André Mignot
Le Chesnay Yvelines, 78157, France
CHU Amiens
Amiens , 80054, France
Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris
Bobigny , 9300, France
CHU de Caen
Caen , 14033, France
Centre Hospitalier Universitaire Grenoble Hopital Michalon
Grenoble Cedex 9 , 38043, France
CHU la Conecption
Marseille , 13005, France
CHU de Nice
Nice , 06202, France
Hopital Saint Louis
Paris , 75010, France
Centre hospitalier Lyon Sud
Pierre-Bénite , 69495, France
Klinikum Frankfurt Hoechst
Frankfurt , 65929, Germany
UniversitatsklinikumUKSH Kiel
Kiel , 24105, Germany
Universitatsklinikum Marburg
Marburg , 35033, Germany
Robert-Bosch- Krankenhaus
Stuttgart , 70376, Germany
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Severance Hospital
Seoul , 03722, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Samsung Medical Center
Seoul , 06351, Korea, Republic of
Zespół Szpitali Miejskich w Chorzowie
Chorzów , 41500, Poland
Uniwersyteckie Centrum Kliniczne Klinika Hematologii i Transplantologii
Gdańsk , 80211, Poland
Katedra i Klinika Hematologii
Wrocław , 50556, Poland
Institut Catala d'Oncologia (ICO) - Hospital Universitari Germans Trias i Pujol
Badalona , 08916, Spain
Hospital Vall d'Hebron
Barcelona , 08035, Spain
MD Anderson Cancer Center
Madrid , 28033, Spain
Hospital Universitario Virgen de la Victoria
Málaga , 29010, Spain
Hospital Son ESPASES
Palma De Mallorca , 07120, Spain
Hospital Clínico Universitario de Salamanca
Salamanca , 37007, Spain
Hospital U. P. La Fe
Valencia , 46026, Spain

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 3

Estimated Enrollment:

200

Study ID:

NCT03504410

Recruitment Status:

Terminated

Sponsor:


Cornerstone Pharmaceuticals

How clear is this clinincal trial information?

×

Introducing, the Journey Bar

Use this bar to access information about the steps in your cancer journey.