Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia

Phase 1

Completed

• Conditions: Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myelomonocytic Leukemia (M4); Adult Pure Erythroid Leukemia (M6b); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia
• Interventions: Drug: bortezomib; Drug: mitoxantrone hydrochloride; Drug: etoposide; Drug: cytarabine; Other: flow cytometry

• Registration Number: NCT01127009
• Lead Sponsor: Case Comprehensive Cancer Center

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 Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2010-05-19
• Study First Submitted QC: 2010-05-19
• Study First Posted: 2010-05-20
• Study Start: 2010-07
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-12
• Last Update Posted: 2015-08-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	mitoxantrone hydrochloride	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.
Arm I	flow cytometry	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.
Arm I	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.
Arm I	etoposide	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.
Arm I	cytarabine	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.

Primary Outcome Measures

Name	Time	Method
MTD of bortezomib	two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment.

Secondary Outcome Measures

Name	Time	Method
Non-dose limiting toxicities	two times a week until Day 28, then every week until Day 45 (+/- 2 days), then 4 wks after treatment.
CR/ CRp rate	repeated 4 weeks after the post-treatment bone marrow aspirate/biopsy.
CD74 antigen expression	to be performed only on the pre-treatment sample

Trial Locations

Locations (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States