Clinical Trial: Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase I Study of Bortezomib in Combination With MEC (Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine) for Relapsed/ Refractory Acute Myelogenous Leukemia (AML)
Brief Summary:
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with mitoxantrone, etoposide, and cytarabine in treating patients with relapsed or refractory acute myeloid leukemia.
Detailed Summary:
PRIMARY OBJECTIVES:
I. To determine the DLT, MTD, and the recommended Phase 2 dose of bortezomib in combination with MEC in patients with relapsed/refractory AML.
SECONDARY OBJECTIVES:
I. To describe the non-dose limiting toxicities associated with bortezomib in combination with MEC in patients with relapsed/refractory AML.
II. To describe any preliminary evidence of clinical activity of this combination (CR rate) in relapsed/refractory AML.
III. To determine the median CD74 antigen expression in patients achieving a response versus those patients not achieving a response.
OUTLINE:
This is a dose-escalation study of bortezomib.
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8 and 11; and mitoxantrone IV, etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6 hours on days 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4-5 weeks.
Sponsor: Case Comprehensive Cancer Center
Current Primary Outcome: MTD of bortezomib [ Time Frame: two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment. ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Non-dose limiting toxicities [ Time Frame: two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment. ]
- CR/ CRp rate [ Time Frame: repeated 4 weeks after the post-treatment bone marrow aspirate/biopsy. ]
- CD74 antigen expression [ Time Frame: to be performed only on the pre-treatment sample ]
Original Secondary Outcome: Same as current
Information By: Case Comprehensive Cancer Center
Dates:
Date Received: May 19, 2010
Date Started: July 2010
Date Completion:
Last Updated: August 12, 2015
Last Verified: August 2015
