Efficacy/Safety of CPI-613 in Combination With HD Cyt. and Mito. vs HD Cyt. and Mito. in Older Patients With R/R AML
- Conditions
- Relapsed/Refractory Acute Myeloid Leukemia
- Interventions
- Drug: CPI-613 + High Dose Cytarabine and MitoxantroneDrug: Fludarabine, Cytarabine, Filgrastim
- Registration Number
- NCT03504410
- Lead Sponsor
- Cornerstone Pharmaceuticals
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CPI-613 + HD Cytarabine and Mitoxantrone CPI-613 + High Dose Cytarabine and Mitoxantrone 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. Control (HAM) and control sub-groups (MEC and FLAG) Fludarabine, Cytarabine, Filgrastim 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 Control (HAM) and control sub-groups (MEC and FLAG) High Dose Cytarabine and Mitoxantrone 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 Control (HAM) and control sub-groups (MEC and FLAG) Mitoxantrone, Etoposide and Cytarabine 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
- Primary Outcome Measures
Name Time Method Complete Remission (CR) 12 months Complete disappearance of all clinical evidence of disease
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (60)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
MD Andrson Cancer Center
🇺🇸Houston, Texas, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Border Medical Oncology Research Unit
🇦🇺Albury, New South Wales, Australia
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Uniwersyteckie Centrum Kliniczne Klinika Hematologii i Transplantologii
🇵🇱Gdańsk, Poland
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Hanuschkrankenhaus der WGKK
🇦🇹Wien, Austria
Universitätsklinik für Innere Medizin
🇦🇹Graz, Austria
Paracelsus Medical University
🇦🇹Salzburg, Austria
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Chao Family Comprehensive Cancer Center (University of California Irvine)
🇺🇸Orange, California, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
University of Iowa-Holden Cancer Care Center
🇺🇸Iowa City, Iowa, United States
Atlantic Health System
🇺🇸Morristown, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Stony Brook University Hospital
🇺🇸Long Island City, New York, United States
University of Texas - Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor Temple (BSW)
🇺🇸Temple, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Calvary Mater Newcastle Hospital
🇦🇺Waratah, New South Wales, Australia
Algemeen Ziekenhuis Sint-Jan
🇧🇪Brugge, Belgium
Clinique Universitaire St Luc
🇧🇪Brussels, Belgium
Centre Hospitalier de Versailles - Hôpital André Mignot
🇫🇷Le Chesnay, Yvelines, France
CHU Amiens
🇫🇷Amiens, France
UN Gent
🇧🇪Gent, Belgium
CHU la Conecption
🇫🇷Marseille, France
CHU de Caen
🇫🇷Caen, France
Centre Hospitalier Universitaire Grenoble Hopital Michalon
🇫🇷Grenoble Cedex 9, France
Service d'Hématologie Clinique, Hôpital Avicenne-APHP-Université Paris
🇫🇷Bobigny, France
Klinikum Frankfurt Hoechst
🇩🇪Frankfurt, Germany
UniversitatsklinikumUKSH Kiel
🇩🇪Kiel, Germany
Hopital Saint Louis
🇫🇷Paris, France
CHU de Nice
🇫🇷Nice, France
Centre hospitalier Lyon Sud
🇫🇷Pierre-Bénite, France
Universitatsklinikum Marburg
🇩🇪Marburg, Germany
Robert-Bosch- Krankenhaus
🇩🇪Stuttgart, Germany
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Zespół Szpitali Miejskich w Chorzowie
🇵🇱Chorzów, Poland
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Katedra i Klinika Hematologii
🇵🇱Wrocław, Poland
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Catala d'Oncologia (ICO) - Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital U. P. La Fe
🇪🇸Valencia, Spain
Hospital Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Son ESPASES
🇪🇸Palma De Mallorca, Spain
Hospital Clínico Universitario de Salamanca
🇪🇸Salamanca, Spain
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
UNC Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States