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

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01673009
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 75
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• 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 1, 2006
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Tumor Volume at 6 Months [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 [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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 65 Years
• 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.

1. 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.

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Indiana University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT01673009
• Other Study ID Numbers: 0512-25
• First Posted: Aug 27, 2012
• Last Update Posted: Apr 6, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Indiana University: Gleevec
• Additional relevant MeSH terms: Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibroma, Plexiform; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Administration of Gleevec
Arm/Group Description	Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients. Gleevec: Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Period Title: Overall Study
STARTED	36
COMPLETED	23
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Administration of Gleevec
Arm/Group Description	Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients. Gleevec: Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Overall Participants	36
Age (Count of Participants)
<=18 years	25 69.4%
Between 18 and 65 years	11 30.6%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	17 47.2%
Male	19 52.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.6%
Not Hispanic or Latino	34 94.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 5.6%
White	32 88.9%
More than one race	0 0%
Unknown or Not Reported	1 2.8%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Tumor Volume at 6 Months
Description	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
Time Frame	baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Administration of Gleevec
Arm/Group Description	Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients. Gleevec: Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Measure Participants	23
Median (95% Confidence Interval) [percentage change of tumor volume]	17

2. Secondary Outcome

Title	Serum Bioactivity
Description	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)
Time Frame	7 days and 1 month

Outcome Measure Data

Analysis Population Description

unable to measure this outcome because assay became unavailable

Arm/Group Title	Administration of Gleevec
Arm/Group Description	Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients. Gleevec: Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
Measure Participants	0

Adverse Events

Time Frame	6 months
Arm/Group Title	Administration of Gleevec
Arm/Group Description	Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients. Gleevec: Gleevec® will be dosed orally 440 mg/m2/day (max 800 mg/day) for pediatric subjects and 800 mg/day for adult patients.
All Cause Mortality
	Administration of Gleevec
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Administration of Gleevec
	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)
Hepatobiliary disorders
liver dysfunction/failure	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Administration of Gleevec
	Affected / at Risk (%)	# Events
Total	12/36 (33.3%)
General disorders
Edema	3/36 (8.3%)	4
Investigations
Neutropenia	2/36 (5.6%)	2
Nervous system disorders
Pain	3/36 (8.3%)	4
Skin and subcutaneous tissue disorders
Rash	4/36 (11.1%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.