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

Phase 3
Terminated
Conditions
Relapsed/Refractory Acute Myeloid Leukemia
Interventions
Drug: CPI-613 + High Dose Cytarabine and Mitoxantrone
Drug: 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
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CPI-613 + HD Cytarabine and MitoxantroneCPI-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)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
Control (HAM) and control sub-groups (MEC and FLAG)High Dose Cytarabine and MitoxantroneHigh 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 CytarabineHigh 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
NameTimeMethod
Complete Remission (CR)12 months

Complete disappearance of all clinical evidence of disease

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (60)

Honor Health Research Institute

🇺🇸

Scottsdale, Arizona, United States

Chao Family Comprehensive Cancer Center (University of California Irvine)

🇺🇸

Orange, California, United States

California Pacific Medical Center

🇺🇸

San Francisco, California, United States

Northwestern Memorial Hospital

🇺🇸

Chicago, Illinois, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

University of Iowa-Holden Cancer Care Center

🇺🇸

Iowa City, Iowa, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Norton Cancer Institute

🇺🇸

Louisville, Kentucky, United States

Atlantic Health System

🇺🇸

Morristown, New Jersey, United States

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Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States

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