NCT02070458

Ixazomib, Mitoxantrone Hydrochloride, Etoposide, and Intermediate-Dose Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 Study of MLN9708 in Combination With MEC (Mitoxantrone, Etoposide, and Intermediate-Dose Cytarabine) for Relapsed/ Refractory Acute Myelogenous Leukemia (AML)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of ixazomib when given in combination with mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine in treating patients with acute myeloid leukemia that is unresponsive to initial induction chemotherapy or recurs following an initial complete remission. Acute myeloid leukemia is a cancer of the bone marrow cells; bone marrow is where blood cells are normally made. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine are standard treatment for relapsed or refractory acute myeloid leukemia. Giving ixazomib with mitoxantrone hydrochloride, etoposide, and intermediate-dose cytarabine may improve the effectiveness of the chemotherapy.

Detailed description

PRIMARY OBJECTIVES: I. To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and the recommended Phase 2 dose of MLN9708 (ixazomib) in combination with mitoxantrone hydrochloride, etoposide, intermediate-dose cytarabine (MEC) in patients with relapsed/ refractory acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To describe the non-dose limiting toxicities associated with MLN9708 in combination with MEC in patients with relapsed/ refractory AML. II. To describe any preliminary evidence of clinical activity of this combination (compete response \[CR\] rate) in relapsed/ refractory AML. III. To determine the median cluster of differentiation (CD)74 antigen expression in patients achieving a response versus those patients not achieving a response. IV. To determine if gene expression profile pre- and post-treatment correlates with response to therapy. OUTLINE: This is a dose-escalation study of ixazomib. Patients receive ixazomib orally (PO) on days 1, 4, 8, and 11, mitoxantrone hydrochloride intravenously (IV), etoposide IV over 1 hour, and intermediate-dose cytarabine IV over 6 hours on days 1-6. After completion of study treatment, patients are followed up for 4-5 weeks.

Conditions

• Recurrent Adult Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	ixazomib	Given PO
DRUG	mitoxantrone hydrochloride	Given IV
DRUG	etoposide	Given IV
DRUG	cytarabine	Given IV

Timeline

• Start date: 2014-10-08
• Primary completion: 2017-03-17
• Completion: 2017-08-15
• First posted: 2014-02-25
• Last updated: 2018-12-13

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study