The goal of this study is to find the safest dose of Pixantrone (BBR 2778) that can be given
to patients with Acute Myelogenous Leukemia (AML). After the safest dose is found, up to an
additional 86 patients will be enrolled. During this part of the study, the safety and
effectiveness will be evaluated.
This is an open label, single center, phase I/II study of pixantrone in patients with
refractory AML. Pixantrone will be administered for three consecutive days on days 1, 2 and
3 of each 21-day cycle, for up to two cycles.
The study has 2 parts; phase I and phase II. In the phase I part of the study, the maximum
tolerated dose (MTD) for pixantrone as a single agent in patients with refractory AML will
be determined. In the phase II part of the study, up to an additional 86 patients will be
treated at the MTD to assess disease response.
- Patients with morphologically confirmed diagnosis of relapsed AML with
French-American-British (FAB) classification other than M3. Relapse should be
demonstrated by the presence of greater than 5% leukemic blasts in the bone marrow or
reappearance of greater than 5% leukemic blasts in the peripheral blood within 14
days of registration.
Eligible patients include the following:
- Patients with secondary AML, including patients with prior myelodysplastic syndromes
- Patients who were initially unresponsive to induction therapy
- Patients in first or second relapse from prior therapy or hematopoietic stem-cell
- A period of at least 21 days must have elapsed from the completion of prior
chemotherapy (with or without anthracyclines) and investigational agents to the
first dose of treatment in this study, and all acute toxicities from prior
therapy must have resolved (with the exception of alopecia).
- Age >/= 18 years of age, and able to give informed consent.
- ECOG performance status of 0, 1 or 2.
- Bilirubin < 1.5 x institution's upper limit of normal (ULN), AST and ALT < 1.5 x
institution's ULN, creatinine < 2 mg/dL.
- LVEF >/= 50% as measured by MUGA scan or 2-D ECHO within 14 days prior to
registration. Either method is acceptable for measuring LVEF; however, the same
method must be used throughout treatment and follow-up.
- Patients (male or female) of reproductive potential must commit to use adequate
contraception (as defined by the investigator) during study treatment and for 6
months after the last day of study drug administration.
- Patients must have signed an approved informed consent prior to beginning
protocol specific procedures
- Prior treatment with a cumulative dose of doxorubicin or equivalent exceeding 450
mg/m2 according to the following calculation index: X/450 + Y/160 < 1 where X is the
doxorubicin dose in mg/m2 and Y is the mitoxantrone dose in mg/m2.
- Clinical or documented central nervous system (CNS) involvement with AML.
- Any uncontrolled active infection that requires antibiotics.
- History of Human Immunodeficiency Virus (HIV).
- Acute hepatitis, or known chronic hepatitis.
- Unstable cardiovascular conditions, including: cardiac arrhythmias, angina, or
myocardial infarction within the past 6 months.
- Pregnant women or nursing mothers.
- Prior malignancy except: curatively treated basal cell or squamous cell skin cancer,
in situ cervical cancer, adequately treated stage I or II cancer from which the
patient is currently in remission, or any other cancer from which the patient has
been disease-free for 5 years.
- Any condition which, in the judgment of the investigator, would place the patient at
undue risk, interfere with the results of the study, or make the patient otherwise
- Any circumstance at the time of study entry that would preclude completion of the