OK432 (Picibanil) in the Treatment of Lymphatic Malformations

Lymphatic Malformations Clinical Trial

Official title:

A Phase 2, Multicenter, Open Label Study to Evaluate the Efficacy and Safety of OK-432 Immunotherapy in Individuals With Lymphatic Malformations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03427619
• Other study ID #: 201107741
• Status: Completed
• Phase: Phase 2
• Start date: October 5, 2005
• Est. completion date: April 30, 2018

Study information

• Verified date: October 2021
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Standard of care for Lymphatic Malformations has been surgical excision. We have been using OK432/Picibanil (generously supplied by Chugai Pharmaceuticals in Japan) since 1992 with great success for macrocystic disease.

The objective of the study was to provide OK-432 immunotherapy to subjects with macrocystic or mixed (> 50% macrocystic) lymphatic malformations (LMs) and investigate the efficacy and safety of OK 432 as a treatment option in subjects with LMs.

Description:

Lymphatic malformations are uncommon tumors that represent localized malformations in the development of the lymphatic system. They typically present in children under 2 years of age and in almost 50% of the cases, are diagnosed at birth. There is neither a racial nor a sexual tendency. The malformations can occur anywhere on the body, but typically they are in the head/neck area.

Morbidity can be significant. Besides the obvious cosmetic deformity caused by these tumors, there is risk of infection and airway compromise and even obstruction. However, effective therapeutic options are limited. Small lesions can be observed, although spontaneous resolution is unlikely. For larger lesions, surgery has been the traditional form of therapy. In the head and neck, in particular, lymphangiomas typically wrap themselves around major neurovascular structures, making total excision removal difficult, if not impossible, and thus the likelihood of recurrence is quite high. Because of these surgical limitations, alternate therapies have been considered; including cryotherapy, diathermy, and chemical sclerotherapy.

The investigators experience with using the drug for macrocystic disease(large cysts) since 1992 in the United States has been very promising compared to traditional surgery. Recurrence rate to date, has been very minimal as well. (<2%)

After the conclusion of the Phase 2 randomized study, all new subjects who presented with an LM and were eligible for treatment were treated under an open-label protocol for continued access to OK-432. This multicenter, open label study enrolled subjects between September 2005 and November 2017.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: April 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

Inclusion Criteria:

To be eligible to receive OK432 immunotherapy

• Patients must be ages 6 months to 17 years

• Patients must have a macrocystic Lymphatic Malformation

• Patients may have had surgical treatment for their Lymphatic Malformation

• Patients must have an imaging study to confirm the diagnosis of a macrocystic or mixed Lymphatic Malformation An MRI is preferred over a CT scan (an ultrasound may be used between injections if warranted, however an MRI or CT should be done pre and post treatment)

Exclusion Criteria:

• Penicillin allergy

• Women who are pregnant or nursing

• Patients who present with a temperature of 100.5 degrees F or greater

• Patients with mixed hemangioma-lymphangioma lesions

• Patients with a history OR a family history of rheumatic heart disease or post-streptococcal glomerulonephritis

• Patients with hemodynamic instability and respiratory failure

• Patients with a history OR a family history of obsessive-compulsive, tic disorders, or PANDA (pediatric autoimmune neuro-psychiatric disorder associated with streptococcal infections)

• Patients who demonstrate abnormalities in the history, physical examination or laboratory analysis which may indicate significant hepatic, hematologic, or renal disease

• Patients who are not in "good general health" (including patients with congenital disorders, chronic diseases, immunologic dysfunction, transplant recipients)

Related Conditions & MeSH terms

• Congenital Abnormalities
• Lymphangioma
• Lymphatic Abnormalities
• Lymphatic Malformations

Intervention

Drug:
• OK432
OK432 will be injected at dosage of 0.01 to 0.05 mg/mL 6-12 weeks apart up to 4 injections total.

Locations

Country	Name	City	State
United States	The Children's Hospital of Denver	Denver	Colorado
United States	Spectrum Health-SHMG Ear, Nose, & Throat	Grand Rapids	Michigan
United States	Children's ENT of Houston	Houston	Texas
United States	Richard Smith, MD	Iowa City	Iowa
United States	University of Wisconsin Hospital & Clinic	Madison	Wisconsin
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospitals & Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Vanderbilt University Hospital	Nashville	Tennessee
United States	Children's Hospital of the Kings Daughter	Norfolk	Virginia
United States	Oregon Health Sciences University	Portland	Oregon
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Rady Children's Hospital & Health Center San Diego	San Diego	California
United States	SUNY Health Science Center	Syracuse	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Richard JH Smith

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging	Clinical success was defined as having either a complete (90% 100%) or substantial (60% 89%) reduction in lymphatic malformation (LM) volume after treatment. Response was determined using post treatment imaging studies at approximately 1 to 6 months after completion of treatment	1 to 6 Months Post-Therapy
Secondary	Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging	Number of participants who demonstrated a complete (90%-100% reduction in LM volume), substantial (60%-89% reduction in LM volume), intermediate (20%-59% reduction in LM volume), or no (< 20% reduction in LM volume) response 1 to 6 months post-therapy as assessed by imaging	1 to 6 Months Post-Therapy
Secondary	Number of Participants With Investigator-Evaluated Overall Response	Investigator evaluated post-therapy clinical response based on physical exam and/or ultrasound was categorized as "Clinical Improvement" or "No Change" in the size of the cyst.	1 to 6 Months Post-Therapy
Secondary	Change From Baseline in Lesion Volume	Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.	Baseline and 1 to 6 Months Post-Therapy