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Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas (0908-09)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01140360
First Posted: June 9, 2010
Last Update Posted: July 2, 2017
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.
Information provided by (Responsible Party):
Kent Robertson, Indiana University School of Medicine
  Purpose
This is a second Pilot Study to determine the efficacy of Gleevec® in neurofibromatosis (NF1) patients with plexiform neurofibromas using new response assessment modalities with the secondary goals of assessing Gleevec toxicity, and characterizing markers of response. The rationale for this study arises from the response of human and murine NF1 cells to Gleevec® in vitro, the response of a NF1 patient treated with Gleevec® for airway compression by a plexiform neurofibroma with a dramatic response not previously seen in NF1 therapy, and the experience in 37 NF1 patients treated with Gleevec® in the initial pilot study. Gleevec will be dosed orally with a starting dose of 100 mg twice daily for patients with a BSA > 1.8 m2 or 55 mg/m2 twice daily for patients with BSA < 1.8 m2. For patients with a BSA > 1.8 m2 the dose will increase by increments of 100 mg bid every two weeks as tolerated up to a maximum dose of 400 mg bid. For patients with a BSA < 1.8 m2 the dose will increase by increments of 55 mg/m2 bid every two weeks as tolerated up to a maximum dose of 220 mg/m2 bid. Treatment will continue for 6 months with an option to continue for 24 months if the patient is deriving a clinical benefit.

Condition Intervention Phase
Neurofibromatosis Neurofibromas Drug: Gleevec Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas

Resource links provided by NLM:


Further study details as provided by Kent Robertson, Indiana University School of Medicine:

Primary Outcome Measures:
  • Disease Response [ Time Frame: 1 year ]
    To estimate the disease control rate (SD, PR, CR) with Gleevec/Imatinib Mesylate in patients with neurofibromas (NF1). The sum of the longest diameter (LD) for all target lesions will be calculated and reported as the disease measurement. Complete Response (CR) disappearance of target lesions. Partial Response (PR) at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study entry. Progressive Disease (PD) at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment. Stable Disease (SD) neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest disease measurement since the treatment started.


Enrollment: 21
Study Start Date: February 2012
Study Completion Date: December 2016
Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gleevec
Gleevec will be dosed orally with a starting dose of 100 mg twice daily for patients with a BSA > 1.8 m2 or 55 mg/m2 twice daily for patients with BSA < 1.8 m2. For patients with a BSA > 1.8 m2 the dose will increase by increments of 100 mg bid every two weeks as tolerated up to a maximum dose of 400 mg bid. For patients with a BSA < 1.8 m2 the dose will increase by increments of 55 mg/m2 bid every two weeks as tolerated up to a maximum dose of 220 mg/m2 bid.Treatment will continue for 6 months with an option to continue for 24 months if the patient is deriving a clinical benefit.
Drug: Gleevec
Gleevec will be dosed orally with a starting dose of 100 mg twice daily for patients with a BSA > 1.8 m2 or 55 mg/m2 twice daily for patients with BSA < 1.8 m2. For patients with a BSA > 1.8 m2 the dose will increase by increments of 100 mg bid every two weeks as tolerated up to a maximum dose of 400 mg bid. For patients with a BSA < 1.8 m2 the dose will increase by increments of 55 mg/m2 bid every two weeks as tolerated up to a maximum dose of 220 mg/m2 bid.Treatment will continue for 6 months with an option to continue for 24 months if the patient is deriving a clinical benefit.
Other Name: Imatinib Mesylate

  Eligibility

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

Inclusion criteria

  1. Patients > 3 years of age.
  2. Diagnosis of neurofibromatosis type 1 (NF1).
  3. Presence of clinically significant plexiform neurofibromas (biopsy proven if possible with tissue blocks available); defined as 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).
  5. Patients must have a Karnofsky of > 70% or Lansky of > 50% and a life expectancy of > 2 months.
  6. 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.

  7. Patients must be able to swallow whole pills.
  8. 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.
  9. 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 or equal to 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.
  13. Patients who have or anticipate receiving permanent (or semi-permanent) metallic structures attached to their body. (e.g., braces on teeth, body piercings), which their physicians believe will interfere with the MRI.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT01140360


Locations
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Kent Robertson
Investigators
Principal Investigator: Kent Robertson, MD PhD Indiana University
  More Information

Responsible Party: Kent Robertson, Associate Professor of Pediatrics, Indiana University School of Medicine
ClinicalTrials.gov Identifier: NCT01140360     History of Changes
Other Study ID Numbers: NF/Gleevec DOD Trial
0908-09 ( Other Identifier: IUPUI IRB )
First Submitted: June 8, 2010
First Posted: June 9, 2010
Results First Submitted: December 21, 2016
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017
Last Verified: June 2017

Keywords provided by Kent Robertson, Indiana University School of Medicine:
Neurofibromas

Additional relevant MeSH terms:
Neurofibromatoses
Neurofibroma
Nerve Sheath Neoplasms
Neurofibroma, Plexiform
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action


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