Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

A Phase II Study of Gemcitabine/ Mitoxantrone in Patients With Acute Myeloid Leukemia in First Relapse

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00268242
• Other study ID #: CASE-CCF-7725
• Secondary ID: P30CA043703CASE-
• Status: Terminated
• Phase: Phase 2
• First received: December 20, 2005
• Last updated: January 24, 2018
• Start date: January 2006
• Est. completion date: July 2011

Study information

• Verified date: August 2015
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: July 2011
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Bone marrow examination or peripheral blood analysis confirming active acute myeloid leukemia by WHO criteria

• No M3 acute myeloid leukemia

• Not a candidate for allogenic bone marrow transplantation

• Patient must be in first relapse after having received induction chemotherapy

• Received 1 or 2 courses with remission lasting at least 1 month

• Patients with chloromas or leukemia cutis are eligible

• No evidence of leptomeningeal involvement

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

• Liver enzymes (total bilirubin, aspartate aminotransferase (AST) and ALT) = 2.5 times the upper limits of normal

• Liver enzymes = 2.5 are acceptable if physician documents that it is secondary to the disease

• Serum creatinine = 3 mg/dL

• No poorly controlled medical conditions that would seriously complicate compliance with this study

• No other active primary malignancy other than carcinoma in situ of the cervix or basal cell carcinoma of the skin

• No New York Heart Association grade III or IV cardiac problems, defined as congestive heart failure or myocardial infarction within 6 months prior to start of study

• Pregnant or nursing women are ineligible

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study participation

• No documented history of human immunodeficiency virus (HIV) infection

• No history of chronic liver disease

• Ejection fraction = 45%

• No significant history of non-compliance to medical regimens or inability to give reliable informed consent

PRIOR CONCURRENT THERAPY:

• Previous treatment related toxicities should be resolved to grade 1 or better

• No other investigational agents within 14 days prior to the start of study

• No chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to start of study

• No major surgery within 2 weeks prior to start of study

• At least two weeks must have elapsed since the conclusion of radiation therapy and the start of gemcitabine hydrochloride, provided the acute effects of radiation treatment have been resolved

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Gemcitabine Hydrochloride
10 mg/m2/ min IV for 12 hours
• Mitoxantrone Hydrochloride
12 mg/m2/day IV (administer over 30-60 minutes) on Day 1, 2 and 3

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
The Cleveland Clinic	Duke University, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate	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).	4 Weeks
Primary	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.
Secondary	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.
Secondary	Laboratory Correlates: Immunohistochemistry	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)	Baseline
Secondary	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.
Secondary	Percentage of Patients Making it to Bone Marrow Transplant.	Assessing the number of patients who were able to have protocol treatment and have a bone marrow transplant after treatment.	After completion of protocol therapy