NCT00882076

Clofarabine, Etoposide, and Mitoxantrone for Relapsed and Refractory Acute Leukemias

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Milton S. Hershey Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to establish toxicity and a maximum tolerated dose recommended phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias. The investigators will observe responses with these therapy agents and assess the impact of Clofarabine interacting with Etoposide in induction of DNA strand breaks.

Detailed description

This will be a phase I study with a standard 3x3 design. Patients will proceed to treatment through a series of cohorts with the three drugs being delivered over five days beginning with a dose of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-3, and clofarabine at 20 mg/m2 IV on days 2-6. Presuming this and subsequent cohorts are tolerable and no more than 1 patient per cohort develops DLT, MTD patients will be treated in cohorts of 3-6 patients up to a final dose level of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-5, and Clofarabine at 30 mg/m2 IV on days 2-6. Patients failing to enter remission may receive 4 days of therapy with Etoposide 100 mg/m2 on days 1-4,Mitoxantrone 8 mg/m2 days 1-2 or 1-4,and Clofarabine at 20-30 mg/m2 IV on days 1-4. According to established definitions for dose limiting toxicity a recommended phase II dose will be established. After this is established the final cohort will be expanded to 15 patients.

Conditions

• Leukemia

Interventions

Type	Name	Description
DRUG	Clofarabine	For Treatment Clofarabine will be administered on Days 2-6 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Clofarabine will be administered on Days 1-4 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1).
DRUG	Mitoxantrone	For Treatment Mitoxantrone will be administered on Days 1-3 at the dose of 8mg/m2 in Cohort 1, 2, 3 and on Days 1-5 for Cohort 4 and on Days 1-3 8mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Mitoxantrone will be administered on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 1, 2 and 3 and on Days 1-4 (4 doses) at the dose of 8mg/m2 in Cohort 4, and on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1).
DRUG	Etoposide	For Treatment Etoposide will be administered on Days 1-5 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Treatment Cohort 1). For Retreatment Etoposide will be administered on Days 1-4 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Retreatment Cohort 1).

Timeline

• Start date: 2009-03-01
• Primary completion: 2011-03-01
• Completion: 2011-03-01
• First posted: 2009-04-16
• Last updated: 2019-07-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study