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A Phase II Study Of Gleevec (Imatinib Mesylate Formerly Known as STI-571) In Patients With Myelofibrosis

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

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Trial Information

A Phase II Study Of Gleevec (Imatinib Mesylate Formerly Known as STI-571) In Patients With Myelofibrosis


I. To determine the response rate (complete and partial) to STI-571 in patients with

II. To determine the safety of STI-571 in patients with myelofibrosis.


I. To determine the effects of STI-571 on bone marrow morphology (including effects on
marrow fibrosis, osteosclerosis and cellularity) in patients with myelofibrosis.

II. To assess the effects of STI-571 on surrogate biologic endpoints including PDGFR
expression (by immunohistochemistry), PDGFR signaling, and circulating progenitor (CD34
positive) cells.

III. To determine the effects of STI-571 on bone marrow cytogenetics in patients with an
abnormal karyotype.

OUTLINE: This is a multicenter study. Patients are stratified according to Dupriez risk
score (low vs intermediate vs high).

Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat
every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

- Patients must have histologic confirmation of one of the following diseases-

- Myeloid metaplasia with myelofibrosis (this includes all subtypes- chronic
idiopathic myelofibrosis or agnogenic myeloid metaplasia, post thrombocythemic
and post polycythemic myelofibrosis) or

- Chronic myelomonocytic leukemia (CMMOL) with t(5;12)(q31-33;p12) or TEL-PDGFRβ
rearrangement; patients with CMMOL and the t(5;7)(q31-33;q11.2) or other
chromosomal translocations resulting in activation of PDGFR will also be

- Patients must have anemia (hemoglobin < 11 g/dL) or palpable splenomegaly
(measured in cm from costal margin- to eligible); patients with palpable
splenomegaly must have spleen size documented ultrasonographically as well; they
must also meet standard diagnostic criteria for MMM* or CMMOL; patients with MMM
must have thrombocytopenia (platelet count < 100 x 10^9/L) to be eligible; they
must be Philadelphia chromosome or (BCR/ABL) rearrangement negative

- Patients with CMMOL must also have the t(5;12)(q31-33;p12) or TEL-PDGFRβ
rearrangement to be eligible

- The Italian diagnostic criteria for MMM

- Necessary criteria

- Diffuse bone marrow fibrosis

- Absence of the Philadelphia chromosome or BCR-ABL rearrangement in
peripheral blood cells

- Optional criteria

- Splenomegaly of any grade

- Anisopoikilocytosis with tear drop erythrocytes

- Presence of circulating immature myeloid cells

- Presence of circulating erythroblasts

- Presence of clusters of megakaryoblasts and anomalous megakaryocytes in
bone marrow sections

- Myeloid metaplasia

- Diagnosis of MMM is acceptable if the following combinations are present

- The two necessary criteria plus any other two optional criteria when
splenomegaly is present OR

- The two necessary criteria plus any other four optional criteria when
splenomegaly is absent

- Patients may have had prior chemotherapy or radiation therapy including splenic
irradiation; prior therapy with erythropoietin, GCSF or androgenic steroids is also
permitted; there is no limit to number of prior regimens received; at least 4 weeks
must have elapsed since prior chemo, radiation or other therapy

- ECOG performance status =< 2 (Karnofsky >= 60%)

- Total bilirubin < 1.5 X institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal unless due to disease

- Serum creatinine < 2 X institutional upper limit of normal

- Patients must not be pregnant or nursing because STI-571 at the recommended
therapeutic dose may be harmful to the developing fetus or newborn; for this reason
women of child-bearing potential and men must agree to use an effective contraceptive
method; women of reproductive potential must have a negative pregnancy test within 7
days prior to registration; since interactions with oral contraceptives cannot be
excluded at present, male and female patients of reproductive potential must agree to
employ an effective barrier method of birth control throughout the study and for up
to 3 months following discontinuation of study drug

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

- World Health Organization (WHO) diagnostic criteria for CMMOL:

- Persistent peripheral blood monocytosis > 1 x 10^9/L

- Absence of the Philadelphia chromosome or BCR/ABL fusion gene

- Fewer than 20% blasts in the blood or bone marrow

- Dysplasia in one or more myeloid lineages; if myelodysplasia is absent or
minimal, the diagnosis of CMML may still be made if the other criteria (1-3) are
met and:

- An acquired clonal cytogenetic abnormality is present in the marrow cells

- The monocytosis has been persistent for at least 3 months

- Other causes for monocytosis have been excluded

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to STI-571

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

- Pregnant women are excluded from this study because STI-571 is an agent 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 STI-571, STI-571 should not be administered patients who are

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with STI-571; appropriate
studies will be undertaken in patients receiving combination anti-retroviral therapy
when indicated

- Because warfarin is metabolized through the CYP450 system, and since gastrointestinal
bleeding may occur with STI-571, no therapeutic anticoagulation with warfarin will be
permitted in patients participating in this study; as an alternative, therapeutic
anticoagulation may be accomplished using low-molecular weight heparin (e.g. Lovenox)
or heparin

Type of Study:


Study Design:

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

Outcome Measure:

Clinical responses in terms of improvement in anemia and splenomegaly as previously published for myelofibrosis

Outcome Time Frame:

Up to 12 months

Safety Issue:


Principal Investigator

Olatoyosi Odenike

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2002

Completion Date:

Related Keywords:

  • Chronic Myelomonocytic Leukemia
  • Essential Thrombocythemia
  • Polycythemia Vera
  • Primary Myelofibrosis
  • Primary Myelofibrosis
  • Leukemia
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Acute
  • Polycythemia
  • Polycythemia Vera
  • Thrombocythemia, Essential
  • Thrombocytosis



University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470