Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

All Conditions

Wounds and Injuries

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Neurofibromatoses

Neurofibromatosis 1

Neurofibroma

Pseudarthrosis

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Peripheral Nervous System Diseases

Neuromuscular Diseases

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Fractures, Bone

Fractures, Ununited

Neurofibromatosis

Neurofibromatosis Type 1

Congenital Pseudoarthrosis

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.

The INFUSE bone graft, containing BMP-2 on a collagen sponge, will be wrapped around the tibia during the surgical process.

INFUSE Bone Graft (BMP-2)

The control group will receive the standard surgical protocol, without addition of the INFUSE device.

Control Group

Bruce R. Korf, MD, PhD

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.

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.

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

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)

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 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.

Numbers of patients with refracture within 1 year after surgery.

Numbers of patients with refracture over long-term follow up of up to 10 years.

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 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 (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.

The Children's Tumor Foundation

Medtronic

University of Alabama at Birmingham

Principal Investigator

The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures. No participants were randomized to the control group.

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.

INFUSE Bone Graft (BMP-2): The INFUSE bone graft, containing BMP-2 on 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.

Control Group: The control group will receive the standard surgical protocol, without addition of the INFUSE device.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The RUST scale (Radiographic Union Score for Tibial fractures; RUST) is a measure of tibial fracture healing. Score is based on radiographic evaluation of the bone cortex based on AP and lateral xrays. Four cortices of tibial bone are each given a score of 1 to 3, with 1=no healing, 2=some callus present, and 3=healing of the bone cortex. The 4 scores are totaled for a total score range of 4 to 12. For 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 = partial healing, and a score of 4 = no healing.

RUST score

Randomization resulted in 0 participants for the Control Group

In June 2019 at the recommendation of the study protocol chairs, the study was closed for enrollment with plans to terminate the study after the last patient completed study procedures. Therefore limited data is available for analysis.

Karen Cole-Plourde

The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.

RUST Score

Average Time to Healing in Months

Refracture Rate

Long-term Refracture

6 month measure

12 month measure

Ten Meter Timed Walk

Participants were all too young to report on this scale (younger than age 4 years). No results are reported.

Spots Global Cancer Trial Database for congenital pseudarthrosis of tibia