Clinical trial NCT03427619: OK432 (Picibanil) in the Treatment of Lymphatic Malformations
Official title: A Phase 2, Multicenter, Open Label Study to Evaluate the Efficacy and Safety of OK-432 Immunotherapy in Individuals With Lymphatic Malformations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphatic Malformations
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2018-02-09
Enrollment: 275
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All eligible participants receive the actual drug.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging
timeFrame: 1 to 6 Months Post-Therapy
Secondary outcomes:
measure: Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging
timeFrame: 1 to 6 Months Post-Therapy
measure: Number of Participants With Investigator-Evaluated Overall Response
timeFrame: 1 to 6 Months Post-Therapy
measure: Change From Baseline in Lesion Volume
timeFrame: Baseline and 1 to 6 Months Post-Therapy
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital & Health Center San Diego
state: California
city: Denver
country: United States
facility: The Children's Hospital of Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Iowa City
country: United States
facility: Richard Smith, MD
state: Iowa
city: Grand Rapids
country: United States
facility: Spectrum Health-SHMG Ear, Nose, & Throat
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals & Clinics of Minnesota - Minneapolis
state: Minnesota
city: Syracuse
country: United States
facility: SUNY Health Science Center
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Hospital
state: Tennessee
city: Houston
country: United States
facility: Children's ENT of Houston
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the Kings Daughter
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Iowa
name: Richard JH Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: