Clinical trial NCT00268242: Gemcitabine and Mitoxantrone in Treating Patients With Relapsed Acute Myeloid Leukemia
Official title: A Phase II Study of Gemcitabine/ Mitoxantrone in Patients With Acute Myeloid Leukemia in First Relapse
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Duke University
First posted: 2005-12-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete Response Rate
timeFrame: 4 Weeks
measure: Duration of the First Complete Response
timeFrame: 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 outcomes:
measure: Disease-free and Overall Survival
timeFrame: 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.
measure: Laboratory Correlates: Immunohistochemistry
timeFrame: Baseline
measure: White Blood Cell Count at Time of Relapse
timeFrame: After a CR is achieved, patient will be followed at 3 month intervals for disease progression, typically for up to 5 years.
measure: Percentage of Patients Making it to Bone Marrow Transplant.
timeFrame: After completion of protocol therapy
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Anjali Advani, MD
role: STUDY_CHAIR
References: