Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
Condition: Neurofibromatosis
MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform
Intervention: Gleevec
Intervention description: Gleevec® will be dosed orally 440 mg/m^2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 3 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Gleevec

Summary:

      THe primary objective is to estimate the response rate at 6 months to Gleevec® in patients
      with plexiform neurofibromas
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients 3-65 years of age.

          2. Diagnosis of neurofibromatosis (NF1), as outpatients.

          3. Presence of clinically significant plexiform neurofibromas (biopsy proven if possible
             with tissue blocks available); that is tumors that are potentially life threatening or
             are impinging on vital structures or significantly impair the quality of life from
             pain or other symptoms.

          4. Patients must have measurable disease by magnetic resonance imaging (MRI). Patients
             must have a Karnofsky or Lansky Performance score of > 80% and a life expectancy of >
             2 months.

          5. Adequate end organ function, defined as the following:

             total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL, creatinine < 1.5 x ULN, ANC >
             1.5 x 109/L, platelets > 100 x 109/L.

          6. Female patients of childbearing potential must have negative pregnancy test within 7
             days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
             for at least 12 months to be considered of non-childbearing potential. 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.

          7. Written, voluntary informed consent.

        Exclusion criteria:

          1. Patient has received any other investigational agents within 28 days of first day of
             study drug dosing, unless the disease is rapidly progressing.

          2. Patient is < 5 years free of another primary malignancy except: if the other primary
             malignancy is not currently clinically significant nor requiring active intervention,
             or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
             situ. Existence of any other malignant disease is not allowed.

          3. Patient with Grade III/IV cardiac problems as defined by the New York Heart
             Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6
             months of study)

          4. Female patients who are pregnant or breast-feeding.

          5. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes,
             chronic renal disease, or active uncontrolled infection).

          6. Patient has a known brain metastasis. Non-specific CNS changes on MRI/CT
             characteristic of NF1 are allowed, but not known CNS malignancies.

          7. Patient has known chronic liver disease (i.e., chronic active hepatitis, and
             cirrhosis).

          8. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.

          9. Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C)
             prior to study entry, unless the disease is rapidly progressing.

         10. Patient previously received radiotherapy to greater than 25 % of the bone marrow

         11. Patient had a major surgery within 2 weeks prior to study entry.

         12. Patient with any significant history of non-compliance to medical regimens or with
             inability to grant reliable informed consent.