Clinical Trial: CIP-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Granulocytic Sarcoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Open Label Study to Evaluate the Feasibility of CPI-613 Given With High Dose Cytarabine and Mitoxantrone in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Brief Summary: This pilot phase II 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.

Detailed Summary:

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
Sponsor: Wake Forest University Health Sciences

Current Primary Outcome: 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 [ Time Frame: Up to 12 weeks of maintenance therapy ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Complete response [ Time Frame: Up to 3 years ]
    Complete response will be compared to the observed rates in a historical cohort of subjects (CCCWFU 22111). Will use a one-sided exact test for a single proportion, a 0.05 significance level.
  • Early mortality (death within 60 days of beginning of treatment) to the observed rates in a historical cohort of subjects [ Time Frame: Up to 60 days ]
    Will use a one-sided exact test for a single proportion, a 0.05 significance level.
  • Frequency of toxicities experienced by the participants, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 [ Time Frame: Up to 3 years ]
    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.
  • Overall survival [ Time Frame: Time from enrollment on trial to death from any cause, assessed up to 6 months after completion of therapy ]
    Will use Kaplan-Meier estimation to analyze overall survival.
  • Response rate (CR and CRi), assessed by standard criteria for AML [ Time Frame: Up to 3 years ]
    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).


Original Secondary Outcome: Same as current

Information By: Wake Forest University Health Sciences

Dates:
Date Received: June 25, 2015
Date Started: September 2015
Date Completion: September 2018
Last Updated: February 20, 2017
Last Verified: February 2017