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A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1) (NF107-BMP2)

Primary Purpose

NF1, Congenital Pseudarthrosis of Tibia

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
INFUSE Bone Graft (BMP-2)
Control Group
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NF1 focused on measuring Tibial Pseudarthrosis

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of NF1 using the NIH Consensus Conference criteria. In addition to tibial pseudarthrosis, one or more of the following diagnostic criteria for NF1 must be present:
  • Six or more cafe'-au-lait spots (≥ 0.5cm prepubertal; ≥ 1.5cm postpubertal)
  • Freckling in the axilla or groin Optic pathway glioma
  • Two or more iris Lisch nodules
  • Two or more neurofibromas or one plexiform neurofibroma
  • A first-degree relative with NF1
  • Patients must have tibial pseudarthrosis that has the potential to cause significant morbidity. Radiographic findings (AP & lateral leg radiographs) must support the diagnosis of tibial pseudarthrosis with chronic non-union.
  • Age between 2 years and 18 years of age at time of study entry.
  • Performance Level: Karnofsky ≥ 50 percent for patients > 10 years of age and Lansky ≥ 50 percent for patients or ≤ 10 years of age.

Prior Therapy:

  • Patients who have undergone 1 previous surgery for tibial pseudarthrosis repair will be eligible to enter the study if they have refracture.
  • Use of BMP-2 in the prior surgery is permitted, however patients with prior exposure must be screened for antibodies to BMP-2, bovine collagen, and rhBMP-2 neutralizing antibodies.
  • Prior use of BMP-2 is allowed but will be recorded as a possible compounding factor.
  • Patients who have had 2 or more prior surgeries for pseudarthrosis repair are ineligible

Absence of Tumors:

  • Patients must undergo thorough physical examination of the leg undergoing surgery. If physical exam is equivocal for presence of tumors, then a normal MRI of the lower extremity will be required before eligibility is met.
  • If there is evidence of plexiform neurofibroma or nodular neurofibroma of > 3 cm diameter on the ipsilateral leg, then they are ineligible for the study.
  • Organ Function Requirements
  • Adequate bone marrow function defined as:

    • Absolute neutrophil count (ANC) > 1500/
    • µl Platelet count > 100,000/
    • µl Hemoglobin ≥ 10.0 gm/dL

Adequate renal function defined as:

  • maximum serum creatinine of 1.5 mg/dL OR
  • a creatinine clearance≥70ml/min/1.73m2.

Adequate renal function defined as:

  • maximum serum creatinine of 1.5 mg/dL OR
  • a creatinine clearance ≥ 70ml/min/1.73m2.

Adequate liver function defined as:

  • Total bilirubin < 1.5 X upper limit of normal for age, and SGPT (serum glutamic pyruvic transaminase, ALT) < 2 X upper limit of normal for age
  • Serum Vitamin D level ≥ 10 ng/ml

Exclusion Criteria:

  • Lack of documentation for a diagnosis of NF1
  • Tibial fracture without evidence of pseudarthrosis or tibial dysplasia
  • Tibial dysplasia/bowing without fracture or pseudarthrosis
  • Plexiform neurofibroma of any size, or nodular neurofibroma of > 3 cm diameter involving the ipsilateral leg, including the hip
  • If presence of plexiform is suspected but not certain on physical exam, MRI of the leg may be indicated to rule this out.
  • History of MPNST (malignant peripheral nerve sheath tumor) or any malignancy other than asymptomatic and stable optic nerve glioma
  • Optic nerve glioma that has resulted in precocious puberty or visual impairment of any degree
  • Visual impairment from any cause
  • Precocious puberty from any cause
  • Hypertension other than mild essential hypertension controlled with medication
  • Metastatic disease of any kind
  • Inadequate neurovascular status in the involved limb that may jeopardize healing
  • Active or known prior infection at the pseudarthrosis site
  • Active systemic infection
  • Other injury or condition that prevents ambulation or completion of study assessments
  • Two or more prior surgeries for tibial pseudarthrosis
  • Bilateral tibial dysplasia
  • Selection of a surgical approach that does not include prescribed surgical intervention, which must include removal of pseudarthrosis tissue, placement of an intramedullary rod using the Williams approach, and autogenous bone graft from the iliac crest distributed at the osteotomy site
  • Normal ipsilateral fibula without planned fibular osteotomy at time of surgery
  • Allergy to bone morphogenetic protein
  • Allergy to bovine collagen products
  • Positive antibody titers to BMP-2, bovine collagen, or BMP-2 neutralizing antibodies prior to surgery
  • History of using any of the following medications, regardless of dose, for at least 1 month, within 3 months of enrollment: Anabolic agents, Glucocorticoids (does not include inhaled glucocorticoids), Growth hormone, Parathyroid hormone (PTH)
  • Need for postoperative medications that could interfere with bone healing of the implant, such as steroids, (but not including low-dose aspirin or routine perioperative anti-inflammatory drugs)
  • Untreated endocrine abnormality, such as hypothyroidism, parathyroid hormone disorder
  • Severe Vitamin D deficiency with serum 25-OH (hydroxy) Vitamin D < 10 ng/ml (25 nmol/l) Patients with Vitamin D levels < 10 ng/ml may be treated with Vitamin D and reconsidered for enrollment when levels are sufficient
  • Females who are sexually active without use of effective contraception
  • Females who are pregnant or breastfeeding

Sites / Locations

  • The University of Alabama at Birmingham
  • Children's Hospital Los Angeles
  • Children's National Medical Center
  • Children's Lurie Hospital
  • University of Chicago
  • Indiana Unversity
  • Johns Hopkins
  • Children' Hospital Boston and Massachusetts General Hospital
  • Children' Hospital Boston
  • Washington University in St. Louis
  • New York University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia
  • Texas Scottish Rite Hospital for Children
  • University of Utah
  • The Children's Hospital at Westmead

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

INFUSE Bone Graft (BMP-2)

Control Group

Arm Description

Children with NF1 and tibial pseudarthrosis who require surgery will have the INFUSE bone graft added to their surgical protocol. After a standard surgical approach of resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod (of the surgeon's choice) and placement of autogenous bone graft from the iliac crest; in addition, the INFUSE bone graft in the form of a collagen sponge will be wrapped around the tibia during the surgical process.

Children with NF1 and tibial pseudarthrosis who require surgery will receive the standard surgical protocol only. This includes resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod (of the surgeon's choice) and placement of autogenous bone graft from the iliac crest.

Outcomes

Primary Outcome Measures

RUST Score
The RUST scale (Radiographic Union Score for Tibial fractures; RUST) was developed in 2010 as a measure of tibial fracture healing and has been validated in the NF1 population. This was used as the primary outcome measure in this trial. The score is based on radiographic evaluation of the bone cortex based on AP (anterior-posterior) and lateral xrays. Four cortices of tibial bone seen in these views are each given a score of 1 to 3, with 1 representing no healing, 2 representing some callus present, and 3 representing healing of the bone cortex. The 4 scores are totaled, to give a total score range of 4 to 12. For the purpose of this study, a total RUST score of 9 to 12, with at least 2 evaluable cortices having a score of 3, is considered to be healed. Scores of 5 to 8 are considered to represent partial healing, and a score of 4 is considered to be no healing.

Secondary Outcome Measures

Average Time to Healing in Months
Time to healing is determined by RUST scores calculated at 3 month intervals after surgery. The first time point at which a score of 9 to 12 is achieved on the RUST Scale will be considered the time to complete healing. One time point is reported which is the time point of first healing.
Refracture Rate
Numbers of patients with refracture within 1 year after surgery.
Long-term Refracture
Numbers of patients with refracture over long-term follow up of up to 10 years.
Ten Meter Timed Walk
Time (seconds) to perform the Ten Meter Timed Walk. Assessed at 6 and 12 months after surgery. Both 6 month and 12 month reported.
Pain Intensity
Pain Intensity was measured using the Faces Pain Scale-Revised (FPS-R) for patients aged 4 years and older. This is a self-report pain scale, where children chose one of 6 faces to indicate their current pain. Scores range from 0 to 10, with 0 representing no pain (happy face) and 10 representing the most pain.
Quality of Life Score - The Upper Extremity and Physical Function Core Scale
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Quality of Life Score - The Transfer and Basic Mobility Core Scale
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Quality of Life Score - The Sports and Physical Functioning Core Scale
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Quality of Life Score - The Pain/Comfort Core Scale
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Quality of Life Score - The Happiness Core Scale
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Quality of Life Score - The Global Functioning Scale
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.

Full Information

First Posted
March 7, 2016
Last Updated
September 29, 2021
Sponsor
University of Alabama at Birmingham
Collaborators
The Children's Tumor Foundation, Medtronic
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1. Study Identification

Unique Protocol Identification Number
NCT02718131
Brief Title
A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1)
Acronym
NF107-BMP2
Official Title
A Study of INFUSE Bone Graft (Recombinant Human Bone Morphogenetic Protein-2/Absorbable Collagen Sponge) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis 1 (NF1)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
Insufficient enrollment to meet the statistical requirements
Study Start Date
March 1, 2016 (Actual)
Primary Completion Date
June 1, 2020 (Actual)
Study Completion Date
June 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
The Children's Tumor Foundation, Medtronic

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The current study proposes adding BMP-2 (INFUSE), an anabolic agent, at the surgical site of TPA (tibial pseudarthrosis) repair in children with NF1, compared to a control group of patients treated surgically without BMP-2. The following Specific Aims will be addressed: 1) to determine if use of an osteogenic agent (BMP-2) at the time of surgical repair of TPA in NF1 patients will result in improved bone healing; 2) to document safety of BMP-2 in a pediatric NF1 population; and 3) to collect, process, and preserve biologic specimens at the time of surgery for future studies.
Detailed Description
A randomized study will be performed by a multi-center group of the NF Consortium. A total of 54 patients will be randomized for treatment with or without INFUSE Bone Graft at the time of surgical repair. For all patients, a standard surgical procedure will be used, including: resection of pseudarthrosis tissue; placement of a rigid intramedullary rod; and placement of autogenous bone graft from iliac crest. For patients in the BMP group, the INFUSE device containing BMP-2 will in addition be applied intraoperatively to the osteotomy site. Fracture union will be determined by scoring of radiographs (RUST score) for cortical bone fusion and callus formation at the osteotomy site. RUST score at 12 months post-surgery will be the primary outcome measure to determine efficacy. Secondary measures will include determination of time to healing (months); quality of life measures; functional walking measures; and incidence of refracture after surgery. This study, once successfully completed, will determine if use of INFUSE Bone Graft improves healing of tibial pseudarthrosis in NF1 and will document safety issues. Regardless of results, the better performing of the two groups (control or BMP) will be able to serve as a much-needed control arm for future studies of additional targeted therapeutic agents for NF1-related bone disease. An international working group of orthopaedic surgeons and NF specialists has been formed and is committed to successful completion of this trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NF1, Congenital Pseudarthrosis of Tibia
Keywords
Tibial Pseudarthrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
INFUSE Bone Graft (BMP-2)
Arm Type
Active Comparator
Arm Description
Children with NF1 and tibial pseudarthrosis who require surgery will have the INFUSE bone graft added to their surgical protocol. After a standard surgical approach of resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod (of the surgeon's choice) and placement of autogenous bone graft from the iliac crest; in addition, the INFUSE bone graft in the form of a collagen sponge will be wrapped around the tibia during the surgical process.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Children with NF1 and tibial pseudarthrosis who require surgery will receive the standard surgical protocol only. This includes resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod (of the surgeon's choice) and placement of autogenous bone graft from the iliac crest.
Intervention Type
Device
Intervention Name(s)
INFUSE Bone Graft (BMP-2)
Intervention Description
The INFUSE bone graft, containing BMP-2 on a collagen sponge, will be wrapped around the tibia during the surgical process.
Intervention Type
Procedure
Intervention Name(s)
Control Group
Intervention Description
The control group will receive the standard surgical protocol, without addition of the INFUSE device.
Primary Outcome Measure Information:
Title
RUST Score
Description
The RUST scale (Radiographic Union Score for Tibial fractures; RUST) was developed in 2010 as a measure of tibial fracture healing and has been validated in the NF1 population. This was used as the primary outcome measure in this trial. The score is based on radiographic evaluation of the bone cortex based on AP (anterior-posterior) and lateral xrays. Four cortices of tibial bone seen in these views are each given a score of 1 to 3, with 1 representing no healing, 2 representing some callus present, and 3 representing healing of the bone cortex. The 4 scores are totaled, to give a total score range of 4 to 12. For the purpose of this study, a total RUST score of 9 to 12, with at least 2 evaluable cortices having a score of 3, is considered to be healed. Scores of 5 to 8 are considered to represent partial healing, and a score of 4 is considered to be no healing.
Time Frame
12 mos post surgery. The score at 12 mos post surgery will be used to determine success of healing and is the score reported.
Secondary Outcome Measure Information:
Title
Average Time to Healing in Months
Description
Time to healing is determined by RUST scores calculated at 3 month intervals after surgery. The first time point at which a score of 9 to 12 is achieved on the RUST Scale will be considered the time to complete healing. One time point is reported which is the time point of first healing.
Time Frame
Baseline through 12 months post-surgery.
Title
Refracture Rate
Description
Numbers of patients with refracture within 1 year after surgery.
Time Frame
12 months post-surgery
Title
Long-term Refracture
Description
Numbers of patients with refracture over long-term follow up of up to 10 years.
Time Frame
annually, up to 10 years post-surgery
Title
Ten Meter Timed Walk
Description
Time (seconds) to perform the Ten Meter Timed Walk. Assessed at 6 and 12 months after surgery. Both 6 month and 12 month reported.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.
Title
Pain Intensity
Description
Pain Intensity was measured using the Faces Pain Scale-Revised (FPS-R) for patients aged 4 years and older. This is a self-report pain scale, where children chose one of 6 faces to indicate their current pain. Scores range from 0 to 10, with 0 representing no pain (happy face) and 10 representing the most pain.
Time Frame
measured at post-op visits at 6 weeks, 3 mos, 6 mos, and 12 mos after surgery
Title
Quality of Life Score - The Upper Extremity and Physical Function Core Scale
Description
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.
Title
Quality of Life Score - The Transfer and Basic Mobility Core Scale
Description
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.
Title
Quality of Life Score - The Sports and Physical Functioning Core Scale
Description
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.
Title
Quality of Life Score - The Pain/Comfort Core Scale
Description
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.
Title
Quality of Life Score - The Happiness Core Scale
Description
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.
Title
Quality of Life Score - The Global Functioning Scale
Description
Quality of Life (QOL) was measured during the study using the Pediatric Outcome Data Collection Instrument (PODCI), a validated scale developed by the American Academy of Orthopaedic Surgeons to measure outcomes in orthopedic interventions. The Parent-report form, which was used for this study, consists of 86 Likert-format questions, covering 5 domains (Upper extremity and physical function; transfer and basic mobility; sports/physical functioning; pain/comfort; and happiness scales). In addition, a Global Functioning Scale is computed. Scores for each subscale range from 0 to 100, with lower scores representing better quality of life.
Time Frame
Assessed at 6 and 12 months after surgery. Month 12 reported.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of NF1 using the NIH Consensus Conference criteria. In addition to tibial pseudarthrosis, one or more of the following diagnostic criteria for NF1 must be present: Six or more cafe'-au-lait spots (≥ 0.5cm prepubertal; ≥ 1.5cm postpubertal) Freckling in the axilla or groin Optic pathway glioma Two or more iris Lisch nodules Two or more neurofibromas or one plexiform neurofibroma A first-degree relative with NF1 Patients must have tibial pseudarthrosis that has the potential to cause significant morbidity. Radiographic findings (AP & lateral leg radiographs) must support the diagnosis of tibial pseudarthrosis with chronic non-union. Age between 2 years and 18 years of age at time of study entry. Performance Level: Karnofsky ≥ 50 percent for patients > 10 years of age and Lansky ≥ 50 percent for patients or ≤ 10 years of age. Prior Therapy: Patients who have undergone 1 previous surgery for tibial pseudarthrosis repair will be eligible to enter the study if they have refracture. Use of BMP-2 in the prior surgery is permitted, however patients with prior exposure must be screened for antibodies to BMP-2, bovine collagen, and rhBMP-2 neutralizing antibodies. Prior use of BMP-2 is allowed but will be recorded as a possible compounding factor. Patients who have had 2 or more prior surgeries for pseudarthrosis repair are ineligible Absence of Tumors: Patients must undergo thorough physical examination of the leg undergoing surgery. If physical exam is equivocal for presence of tumors, then a normal MRI of the lower extremity will be required before eligibility is met. If there is evidence of plexiform neurofibroma or nodular neurofibroma of > 3 cm diameter on the ipsilateral leg, then they are ineligible for the study. Organ Function Requirements Adequate bone marrow function defined as: Absolute neutrophil count (ANC) > 1500/ µl Platelet count > 100,000/ µl Hemoglobin ≥ 10.0 gm/dL Adequate renal function defined as: maximum serum creatinine of 1.5 mg/dL OR a creatinine clearance≥70ml/min/1.73m2. Adequate renal function defined as: maximum serum creatinine of 1.5 mg/dL OR a creatinine clearance ≥ 70ml/min/1.73m2. Adequate liver function defined as: Total bilirubin < 1.5 X upper limit of normal for age, and SGPT (serum glutamic pyruvic transaminase, ALT) < 2 X upper limit of normal for age Serum Vitamin D level ≥ 10 ng/ml Exclusion Criteria: Lack of documentation for a diagnosis of NF1 Tibial fracture without evidence of pseudarthrosis or tibial dysplasia Tibial dysplasia/bowing without fracture or pseudarthrosis Plexiform neurofibroma of any size, or nodular neurofibroma of > 3 cm diameter involving the ipsilateral leg, including the hip If presence of plexiform is suspected but not certain on physical exam, MRI of the leg may be indicated to rule this out. History of MPNST (malignant peripheral nerve sheath tumor) or any malignancy other than asymptomatic and stable optic nerve glioma Optic nerve glioma that has resulted in precocious puberty or visual impairment of any degree Visual impairment from any cause Precocious puberty from any cause Hypertension other than mild essential hypertension controlled with medication Metastatic disease of any kind Inadequate neurovascular status in the involved limb that may jeopardize healing Active or known prior infection at the pseudarthrosis site Active systemic infection Other injury or condition that prevents ambulation or completion of study assessments Two or more prior surgeries for tibial pseudarthrosis Bilateral tibial dysplasia Selection of a surgical approach that does not include prescribed surgical intervention, which must include removal of pseudarthrosis tissue, placement of an intramedullary rod using the Williams approach, and autogenous bone graft from the iliac crest distributed at the osteotomy site Normal ipsilateral fibula without planned fibular osteotomy at time of surgery Allergy to bone morphogenetic protein Allergy to bovine collagen products Positive antibody titers to BMP-2, bovine collagen, or BMP-2 neutralizing antibodies prior to surgery History of using any of the following medications, regardless of dose, for at least 1 month, within 3 months of enrollment: Anabolic agents, Glucocorticoids (does not include inhaled glucocorticoids), Growth hormone, Parathyroid hormone (PTH) Need for postoperative medications that could interfere with bone healing of the implant, such as steroids, (but not including low-dose aspirin or routine perioperative anti-inflammatory drugs) Untreated endocrine abnormality, such as hypothyroidism, parathyroid hormone disorder Severe Vitamin D deficiency with serum 25-OH (hydroxy) Vitamin D < 10 ng/ml (25 nmol/l) Patients with Vitamin D levels < 10 ng/ml may be treated with Vitamin D and reconsidered for enrollment when levels are sufficient Females who are sexually active without use of effective contraception Females who are pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce R. Korf, MD, PhD
Organizational Affiliation
Univ. of Alabama at Birmingham
Official's Role
Study Chair
Facility Information:
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Children's Lurie Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana Unversity
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Children' Hospital Boston and Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children' Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Facility Name
New York University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19096
Country
United States
Facility Name
Texas Scottish Rite Hospital for Children
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
The Children's Hospital at Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1)

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