Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

Phase 2

Terminated

• Conditions: Leukemia
• Interventions: Drug: Gemcitabine Hydrochloride; Drug: Mitoxantrone Hydrochloride

• Registration Number: NCT00268242
• Lead Sponsor: The Cleveland Clinic

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with mitoxantrone works in treating patients with relapsed acute myeloid leukemia.

Detailed Description

OBJECTIVES:

Primary

* Determine the complete response (CR) rate (CR and incomplete blood count recovery (CRi)) of patients with acute myeloid leukemia in first relapse treated with gemcitabine hydrochloride and mitoxantrone hydrochloride.

Secondary

* Evaluate disease free and overall survival of patients with acute myeloid leukemia in first relapse treated with this particular chemotherapy regimen.

* Assess hematologic and non-hematologic toxicity associated with this regimen.

* Assess laboratory correlates of drug resistance in patients with relapsed acute myeloid leukemia.

* Assess the percentage of patients receiving subsequent bone marrow transplantation.

OUTLINE: This is an open-label, multicenter study.

Patients receive gemcitabine hydrochloride IV over 12 hours on day 1 and mitoxantrone hydrochloride IV over 30-60 minutes on days 1, 2, and 3. After completion of a single course of therapy, patients who achieve a complete response may receive 1 additional course of therapy at the discretion of the treating physician.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Timeline

• Study First Submitted: 2005-12-20
• Study First Submitted QC: 2005-12-20
• Study First Posted: 2005-12-22
• Study Start: 2006-01
• Primary Completion: 2010-08
• Study Completion: 2011-07
• Results First Submitted: 2015-06-03
• Status Verified: 2015-08
• Results First Submitted QC: 2015-08-30
• Results First Posted: 2015-10-05
• Last Update Submitted: 2018-01-24
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine + Mitoxantrone	Gemcitabine Hydrochloride	Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m\^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m\^2/day I.V. on days 1, 2, and 3.
Gemcitabine + Mitoxantrone	Mitoxantrone Hydrochloride	Gemcitabine Hydrochloride as administered as a continuous intravenous infusion (I.V.) at 10mg/m\^2/minute for 12 hours, starting on Day 1. Mitoxantrone Hydrochloride was given at a dose of 12mg/m\^2/day I.V. on days 1, 2, and 3.

Primary Outcome Measures

Name	Time	Method
Duration of the First Complete Response	After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
Complete Response Rate	4 Weeks	Assumptions/ hypothesis: A Complete Response (CR) rate of 30% or less is unacceptable, and 50% or more is promising. A two-stage design will be used. Initially, 18 patients will be enrolled. If 5 or fewer achieve CR, the study will be stopped. Otherwise, an additional 22 patients will be accrued. Accrual was not halted while follow-up of the first 18 evaluable patients was under way. Therefore, 24 patients were enrolled. Four weeks is anticipated for observation for response. Only 5 patients (21%) achieved a CR and therefore, the study was terminated. Since response was assessed using the International Working Group criteria, a complete response was determined by Morphologic complete remission: A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of ≥ 100,000/μL, a cytogenic CR and a morphologic CR with incomplete blood count recovery (CRi).

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Making it to Bone Marrow Transplant.	After completion of protocol therapy	Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment.
Disease-free and Overall Survival	After a CR is achieved, patients are followed at 3 month intervals for disease progression and survival. If a patient has disease progression after achieving a CR, survival will be captured at 6 month intervals, typically for up to 5 years.
Laboratory Correlates: Immunohistochemistry	Baseline	Percentage of patients who had a moderate-strong (2-3+) expression of multidrug resistance (MDR) genes by immunohistochemistry.; * Multidrug resistance gene 1 (MDR1); * Equilibrative nucleoside transporter 2(SLC29A2)
White Blood Cell Count at Time of Relapse	After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years.

Trial Locations

Locations (2)

Duke Comprehensive Cancer Center; 🇺🇸 Durham, North Carolina, United States

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