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Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01673009
Recruitment Status : Completed
First Posted : August 27, 2012
Results First Posted : April 6, 2016
Last Update Posted : April 6, 2016
Information provided by (Responsible Party):
Indiana University

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

Condition or disease Intervention/treatment Phase
Neurofibromatosis Drug: Gleevec Phase 2

Detailed Description:
This is an open-label Phase II Study to determine the efficacy of Gleevec® in neurofibromatosis (NF1) patients with plexiform neurofibromas with the secondary goals of determining the toxicity, and tumor markers in this genetically defined population. The rationale for this study arises from the response of human and murine NF1 cells to Gleevec® in vitro and the response of a single NF1 patient treated with Gleevec® for airway compression by a plexiform neurofibroma with a dramatic response not previously seen in NF1 therapy. The plan of therapy will include oral dosing of Gleevec® at 440 mg/m^2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients. (with 25% dose reduction for significant toxicity). Treatment will continue for 6 months with an option to continue as long as the patient remains on study provided the patient shows benefit from treatments with Gleevec® and there are no safety concerns.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
Study Start Date : May 2006
Actual Primary Completion Date : December 2011
Actual Study Completion Date : August 2012

Arm Intervention/treatment
Experimental: Administration of Gleevec
Gleevec® will be dosed orally 440 mg/m^2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Drug: Gleevec
Gleevec® will be dosed orally 440 mg/m^2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.

Primary Outcome Measures :
  1. Percent Change From Baseline in Tumor Volume at 6 Months [ Time Frame: baseline to 6 months ]
    Volumetric measures were performed using MRI scan analysis. Response criteria include greater than 20 percent decrease in tumor volume as responsive. Greater than 20 percent increase in tumor volume as tumor progression. Less then 20 percent increase or decrease in tumor volume is stable disease

Secondary Outcome Measures :
  1. Serum Bioactivity [ Time Frame: 7 days and 1 month ]
    The investigators will quantitate the biologic activity of patient serum on fibroblast proliferation, migration, and collagen synthesis pre and post-Gleevec (7 days and 1 month)

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01673009

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United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Indiana University Identifier: NCT01673009    
Other Study ID Numbers: 0512-25
First Posted: August 27, 2012    Key Record Dates
Results First Posted: April 6, 2016
Last Update Posted: April 6, 2016
Last Verified: April 2016
Keywords provided by Indiana University:
Additional relevant MeSH terms:
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Neurofibromatosis 1
Neurofibroma, Plexiform
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action