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

Phase 2
18 Years
Not Enrolling
Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis

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Trial Information

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


I. To evaluate the response rate in MMM patients treated with R115777. II. To evaluate the
toxicity of R115777 in patients with MMM.


I. To evaluate the benefit of therapy with R115777 in alleviating disease-associated anemia
in patients with MMM.

II. To evaluate the benefit of R115777 in reducing palpable splenomegaly in patients with

III. To evaluate the effect of R115777 on the hypercatabolic symptoms from MMM. IV. To
evaluate the effect of R115777 on the pathologic increase in circulating myeloid progenitors
in MMM patients through baseline measurement and measurement after the first cycle.

V. To correlate response/relapse with in vitro myeloid colony sensitivity to R115777 at the
time of either response or relapse.

VI. To evaluate the effect of R115777 on bone marrow histologic features of MMM including
osteosclerosis, reticulin fibrosis, and angiogenesis (through serial bone marrow microvessel
density grading).

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days
for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for
up to 2 years.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 15

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed response defined as the objective status of complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 4 weeks apart

Outcome Description:

Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Ruben Mesa

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

August 2002

Completion Date:

Related Keywords:

  • Essential Thrombocythemia
  • Polycythemia Vera
  • Primary Myelofibrosis
  • Primary Myelofibrosis
  • Metaplasia
  • Polycythemia
  • Polycythemia Vera
  • Thrombocythemia, Essential
  • Thrombocytosis



Mayo Clinic Rochester, Minnesota  55905