A Phase II Trial of R115777 in Myelofibrosis With Myeloid Metaplasia (MMM)

Inclusion Criteria:

- Histopathologic confirmation (on bone marrow trephine and aspirate) of myelofibrosis
with myeloid metaplasia by a pathologist/hematologist at the registering institution;
included in the diagnosis of MMM are AMM (agnogenic myeloid metaplasia), PPMM
(post-polycythemic myeloid metaplasia), and PTMM (post-thrombocythemic myeloid
metaplasia); the bone marrow should show the presence of reticulin fibrosis, and the
peripheral blood smear should show the presence of leukoerythroblastosis and
dacrocytosis

- Bone marrow showing no evidence of other conditions associated with myelofibrosis,
such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast
cell disease, acute leukemia (including M7 type), or acute myelofibrosis

- Bone marrow chromosome analysis or peripheral blood or bone marrow Fluorescent In
Situ Hybridization (FISH) showing absence of chromosomal translocation t(9:22); prior
demonstration is sufficient for enrollment purposes

- At least one of the following:

- Anemia evidenced by hemoglobin < 10 g/dL

- Palpable hepato-splenomegaly

- ANC ≥ 750/mm^3

- PLT ≥ 100,000/mm^3

- Total bilirubin (direct if total elevated) ≤ UNL

- Alkaline phosphatase =< 3 x UNL (unless felt to be secondary to disease)

- AST ≤ 2.5 x UNL

- Creatinine =< 1.5 x UNL

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

- Willingness to follow the schedule for returning to the registering P2C institution
(monthly) while receiving protocol treatment

- ECOG performance status 0, 1, or 2

Exclusion Criteria:

- Any of the following as this regimen may be harmful to a developing fetus or nursing
child:

- Pregnant women

- Breastfeeding women

- Men or women of childbearing potential or their sexual partners who are
unwilling to employ adequate contraception (condoms, diaphragm, birth control
pills, injections, intrauterine device [IUD], surgical sterilization,
subcutaneous implants, or abstinence, etc.)

- NOTE: The effects of the agent(s) on the developing human fetus at the
recommended therapeutic dose are unknown

- Use of cytotoxic chemotherapy or other myelosuppressive agents within =< 2 weeks
prior to study entry

- Uncontrolled intercurrent illness or any co-morbid condition that would limit
compliance with study requirements or with which the use of R115777 is felt to be
potentially harmful; such conditions include, but are not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia, or

- Psychiatric illness/social situations

- Other concurrent therapy directed at the disease (including Thalidomide) or use of
erythropoietin while enrolled in this study; such agents must be discontinued at the
time of or prior to study entry

- Known quinolone sensitivity