This pilot phase I trial studies how well CPI-613 (6,8-bis\[benzylthio\]octanoic acid), cytarabine, and mitoxantrone hydrochloride work in treating patients with acute myeloid leukemia or granulocytic sarcoma (a malignant, green-colored tumor of myeloid cells \[a type of immature white blood cell\]) that has returned (relapsed) or that does not respond to treatment (refractory). 6,8-bis(benzylthio)octanoic acid is thought to kill cancer cells by turning off their mitochondria. Mitochondria are used by cancer cells to produce energy and are the building blocks needed to make more cancer cells. By shutting off these mitochondria, 6,8-bis(benzylthio)octanoic acid deprives the cancer cells of energy and other supplies that they need to survive and grow in the body. Drugs used in chemotherapy, such as cytarabine and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving 6,8-bis(benzylthio)octanoic acid together with cytarabine and mitoxantrone hydrochloride may kill more cancer cells.
PRIMARY OBJECTIVES: I. To determine the feasibility of CPI-613 when administered with high dose cytarabine, and mitoxantrone (mitoxantrone hydrochloride) in all three phases of salvage therapy (induction, consolidation and maintenance). SECONDARY OBJECTIVES: I. To observe the response rate (complete remission \[CR\], and CR with incomplete recovery \[CRi\]) of CPI-613 in combination with high dose cytarabine and mitoxantrone. II. To observe the overall survival of patients treated with CPI-613 in combination with high dose cytarabine and mitoxantrone in induction, consolidation and maintenance. III. To monitor toxicities experienced by patients treated with CPI-613 in combination with high dose cytarabine and mitoxantrone in induction, consolidation and maintenance. OUTLINE: SALVAGE INDUCTION COURSE 1: Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5, cytarabine IV over 3 hours every 12 hours starting on day 3 for 5 doses, and mitoxantrone hydrochloride IV over 15 minutes after the first, third, and fifth doses of cytarabine. SALVAGE INDUCTION COURSE 2 (OPTIONAL, AT DISCRETION OF TREATING PHYSICIAN): Patients receive 6,8-bis(benzylthio)octanoic acid, cytarabine, and mitoxantrone hydrochloride as in course 1 or an abbreviated second course at the discretion of the treating physician. In the abbreviated course, patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-3, cytarabine IV over 3 hours every 12 hours starting on day 2 for 3 doses, and mitoxantrone hydrochloride IV over 15 minutes after the first and third cytarabine doses. SALVAGE CONSOLIDATION: Patients achieving response receive up to 2 courses of the abbreviated course of 6,8-bis(benzylthio)octanoic acid, high dose cytarabine, and mitoxantrone hydrochloride. Patients achieving response may undergo stem cell transplant at the discretion of the treating physician. Patients may proceed to maintenance after 1, 2 or no courses of consolidation at the discretion of the treating physician. MAINTENANCE THERAPY: Patients achieving response receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Given IV
Given IV
Undergo stem cell transplant
Given IV
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, United States
Feasibility of Administering CPI-613 in Combination With High Dose Cytarabine and Mitoxantrone During Induction, Consolidation and Maintenance Therapies, Defined as Percentage of Patients Eligible for Maintenance Therapy Who Complete at Least 3 Courses
Feasibility is determined by the percentage of patients eligible for maintenance therapy who complete at least 3 cycles, if ≥50% of eligible patients complete 3 cycles of maintenance therapy we will consider this regimen feasible for future study.
Time frame: Up to 12 weeks of maintenance therapy
Frequency of Toxicities Experienced by the Participants, Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0
The frequency of toxicities experienced by the participants will be presented by type and grade in an effort to monitor and report safety of the treatment. Showing grade 2 and greater event and the highest grade of each type per participant so that a participant is only evaluated once per toxicity type. Reporting events where at least 10% (n=5) of study participants reported a grade 2 or greater event.
Time frame: Up to 6 months
Overall Survival
Will use Kaplan-Meier estimation to analyze overall survival.
Time frame: Time from enrollment on trial to death from any cause, assessed up to 30 months after completion of therapy
Response Rate (CR and CRi), Assessed by Standard Criteria for AML
Confidence intervals will be calculated around the estimates of the response rate (CR and CRi). Assuming a response rate of 0.5, with 50 participants, 95 percent confidence intervals can be created with a 0.14 margin of error (0.36, 0.64).
Time frame: Up to 3 years
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