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

NCT02718131 | Terminated Results DMC

• 4 other identifiers: NF107W81XWH-12-1-0155G140004507821
• Study Type: interventional
• Target: 5
• Locations: 2 countries
• Sites: 16

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.

Conditions

NF1; Congenital Pseudarthrosis of Tibia

Keywords

Tibial Pseudarthrosis

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (11)

• Average Time to Healing in Months

  Baseline through 12 months post-surgery.

• Refracture Rate

  12 months post-surgery

• Long-term Refracture

  annually, up to 10 years post-surgery

• Ten Meter Timed Walk

  Assessed at 6 and 12 months after surgery. Month 12 reported.

• Pain Intensity

  measured at post-op visits at 6 weeks, 3 mos, 6 mos, and 12 mos after surgery

Study Arms (2)

INFUSE Bone Graft (BMP-2)

ACTIVE COMPARATOR

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.

Device: INFUSE Bone Graft (BMP-2)

Control Group

PLACEBO COMPARATOR

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.

Procedure: Control Group

Interventions

INFUSE Bone Graft (BMP-2) DEVICE

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)

Control Group PROCEDURE

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

Control Group

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• The Children's Tumor Foundation: collaborator
• Medtronic: collaborator

Study Sites (16)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Lurie Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana Unversity

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Children' Hospital Boston and Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Children' Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19096, United States

Location

Texas Scottish Rite Hospital for Children

Dallas, Texas, 75235, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

MeSH Terms

Interventions

Control Groups

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Limitations and Caveats

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.

Results Point of Contact

• Title: Karen Cole-Plourde
• Organization: University of Alabama at Birmingham

kplourde@uab.edu

205-934-5140

Study Officials

• Bruce R. Korf, MD, PhD

  Univ. of Alabama at Birmingham

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 7, 2016
• First Posted: March 24, 2016
• Study Start: March 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: October 27, 2021
• Results First Posted: October 27, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); AU (1)