Phase I Trial of R115777 (NSC 702818) in Relapsed, Refractory or High Risk Myeloid Leukemia

Inclusion Criteria:

- Adult patients with acute myeloid leukemia (AML), excluding the M3 subtype (acute
promyelocytic leukemia), that are not likely to respond to conventional therapy,
including:

- Relapsed or refractory AML after one to three prior induction regimens (not
counting consolidation therapies while in CR, such as autologous transplant),

- Newly diagnosed AML in patients up to age-70 with poor risk features
(unfavorable cytogenetics or findings suggestive of prior myelodysplasia) not
fit for standard induction therapy, and

- Newly diagnosed AML patients age 70 - 75 not fit for standard therapy (without
history of prior myelodysplastic syndrome [MDS])

- Bone marrow and peripheral blood studies must be available for confirmation of
diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related
tyrosine kinase 3 [Flt-3] status) will be obtained as per standard practice

- Patients with active central nervous system (CNS) leukemia are NOT eligible

- Performance status of 60% or greater by the Karnofsky scale

- If induction chemotherapy has been attempted, a minimum of 4 weeks must have elapsed
since the completion of prior chemotherapy in order to be eligible for this study;
hydroxyurea for control of blasts is not counted as chemotherapy, and may be given up
until 24 hours before starting R115777

- Patients may have had prior autologous transplant; they must be at least 100 days
post transplant, and have had recovery of their counts with ANC > 1000 and platelets
greater than 100K at some point post transplant, and be without active CMV or fungal
disease

- Patients may have received prior radiation therapy as part of a transplant
conditioning regimen; radiotherapy must have been completed at least 100 days prior
to starting on R115777

- There are no minimum hematological parameter requirements prior to the first two
cycles of R115777, as patients with AML and MDS are understood to have low ANC and
platelet counts when the disease is active; however, patients with WBC greater than
30,000 will receive hydroxyurea to reduce WBC to below 30,000 at which point they may
begin treatment with R115777

- A pretreatment calculated creatinine clearance (absolute value) of >= 60 ml/minute or
serum creatinine of < 1.5 x upper limit of normal is required

- Serum bilirubin =< 2.0 mg/dl

- SGOT and SGPT =< 2.5 times the institutional upper limits of normal

- Any condition causing inability to swallow pills given by mouth will render patients
ineligible for the trial

- There must be no plans for the patient to receive concurrent hormonal, biologic, or
radiation therapy

- Patients eligible, at the time of starting the drug, for curative therapeutic
approaches (such as allogeneic transplant) are not eligible for the trial; however,
patients who achieve CR or PR as a result of R115777 may go on to allogeneic
transplant

- Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines

- Prior to the first patient registration, the notification of institutional review
board approval for this study must be provided to the Data Coordinating Center at
City of Hope

- Antacids are allowed but must not be taken concurrently with R115777; (there must be
at least 2 hours between antacid intake and R115777 dosing)

- Pregnant or lactating women are excluded from this trial; all patients of
child-bearing potential, both male and female, must be advised to practice adequate
contraception; premenopausal women must have a negative pregnancy test prior to entry
on this study