Overview

SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

Status:
Completed
Trial end date:
1969-12-31
Target enrollment:
0
Participant gender:
All
Summary
Phase I trial to study the effectiveness of SB-715992 in treating patients who have acute leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes. Drugs used in chemotherapy, such as SB-715992, work in different ways to stop cancer cells from dividing so they stop growing or die
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Criteria
Inclusion Criteria:

- Patients must have acute myelogenous or acute lymphoblastic leukemia refractory to
primary standard induction therapy; relapsed/refractory acute leukemia; chronic
myelogenous leukemia in blast crisis are eligible at diagnosis or after failing
aggressive induction chemotherapy (providing they are refractory to imatinib); acute
leukemia secondary to preexisting hematologic condition or prior chemotherapy are
eligible at diagnosis or after failing aggressive induction chemotherapy, advanced
myelodysplastic syndrome (RAEB or RAEB-2 providing they are neutropenic or transfusion
dependent); patients with de-novo acute leukemia who are not eligible for aggressive
standard induction chemotherapy due to advanced age or serious comorbid medical or
psychiatric conditions, patients above age 60 with de-novo AML and unfavorable
cytogenetics

- At least 2 weeks must have elapsed between completion of most recent cytotoxic
chemotherapy, or biologic therapy except for hydroxyurea or corticosteroids or
Imatinib (24 hours); patients who have previously received an autologous stem cell
transplant are allowed providing a minimum of 3 months has elapsed from transplant
(T0) and patient has recovered from transplant associated toxicities; patients who
have had prior allogeneic stem cell transplant are not eligible; a minimum of five
days must have elapsed since administration of granulocyte or granulocyte-macrophage
colony-stimulating factor and a minimum of 2 weeks if Neulasta; minimum of 2 weeks
since administration of gemtuzumab, ozogamicin (Mylotarg), minimum of 4 weeks for
prior investigational agents

- ECOG performance status =< 2 (Karnofsky >= 50%)

- Life expectancy of at least 4 weeks

- Direct serum bilirubin =< 1.5 mg/dl

- AST(SGOT)/ALT(SGPT) < 3 X institutional upper limit of normal

- Creatinine =< 1.5 X institutional upper limit of normal

- The effects of SB-715992 on the developing human fetus are unknown; for this reason
and because mitotic inhibitors are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry and for the duration of study
participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients may not have received any other investigational agents within 28 days of
study entry

- Patients may not receive any other anti-cancer therapy (cytotoxic, biologic,
radiation, or hormonal other than for replacement) while on this study

- Prohibited medications: SB-715992 is a moderate to significant in vitro inhibitor of
CYP3A4; the following lists of medications/substances are moderate to significant
inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may
alter study drug exposure; the use of these medications/substances within 14 days (>=
6 months for amiodarone) prior to the administration of the first dose of SB-715992
through discontinuation from the study is prohibited

- Inhibitors of CYP3A4:

- Antibiotics: clarithromycin, erythromycin, troleandomycin

- Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day),
voriconazole

- Antidepressants: nefazodone, fluvoxamine

- Calcium channel blockers: verapamil, diltiazem

- Miscellaneous: amiodarone*, grapefruit juice, bitter orange; *use of amiodarone
within 6 months prior to the administration of the first dose of SB-715992 is
prohibited

- Inducers of CYP3A4:

- Anticonvulsants: phenytoin, carbamazepine, phenobarbital, oxcarbazepine

- Antibiotics: rifampin, rifabutin, rifapentine

- Miscellaneous: St. John's wort, modafinil

- Patients with suspected or proven CNS leukemia (diagnostic lumbar puncture not
required before enrollment)

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to SB-715992

- Uncontrolled intercurrent illness including, but not limited to ongoing or active or
poorly controlled infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric
illness/social situations that would limit compliance with study requirements

- Patients with pre-existing neuropathy of grade 2 or higher are not eligible to
participate

- Pregnant women are excluded from this study because SB-715992 is a mitotic inhibitor
with the potential for teratogenic or abortifacient effects; because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with SB-715992, breastfeeding should be discontinued if the
mother is treated with SB-715992

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, HIV-positive patients are excluded
from this study