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OK432 (Picibanil) in the Treatment of Lymphatic Malformations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03427619
Recruitment Status : Completed
First Posted : February 9, 2018
Results First Posted : October 28, 2021
Last Update Posted : November 23, 2021
Information provided by (Responsible Party):
Richard JH Smith, University of Iowa

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.

Condition or disease Intervention/treatment Phase
Lymphatic Malformations Drug: OK432 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 275 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All eligible participants receive the actual drug.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open Label Study to Evaluate the Efficacy and Safety of OK-432 Immunotherapy in Individuals With Lymphatic Malformations
Actual Study Start Date : October 5, 2005
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: OK432 (Picibanil)
There is no control in this study. All participants will receive the actual drug -OK432. With each injection they may receive 0.01 to 0.05mg/mL 6-12 weeks apart up to 4 injections total.
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.
Other Name: Picibanil

Primary Outcome Measures :
  1. Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging [ Time Frame: 1 to 6 Months Post-Therapy ]
    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

Secondary Outcome Measures :
  1. Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging [ Time Frame: 1 to 6 Months Post-Therapy ]
    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

  2. Number of Participants With Investigator-Evaluated Overall Response [ Time Frame: 1 to 6 Months Post-Therapy ]
    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.

  3. Change From Baseline in Lesion Volume [ Time Frame: Baseline and 1 to 6 Months Post-Therapy ]
    Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03427619

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United States, California
Rady Children's Hospital & Health Center San Diego
San Diego, California, United States, 92123
United States, Colorado
The Children's Hospital of Denver
Denver, Colorado, United States, 80218
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Iowa
Richard Smith, MD
Iowa City, Iowa, United States, 52242
United States, Michigan
Spectrum Health-SHMG Ear, Nose, & Throat
Grand Rapids, Michigan, United States, 49546
United States, Minnesota
Children's Hospitals & Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, New York
SUNY Health Science Center
Syracuse, New York, United States, 13210
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Tennessee
Vanderbilt University Hospital
Nashville, Tennessee, United States, 37232
United States, Texas
Children's ENT of Houston
Houston, Texas, United States, 77030
United States, Virginia
Children's Hospital of the Kings Daughter
Norfolk, Virginia, United States, 23507
United States, Wisconsin
University of Wisconsin Hospital & Clinic
Madison, Wisconsin, United States, 53279
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Richard JH Smith
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Principal Investigator: Richard JH Smith, MD University of Iowa
  Study Documents (Full-Text)

Documents provided by Richard JH Smith, University of Iowa:
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Responsible Party: Richard JH Smith, Principal Investigator, University of Iowa Identifier: NCT03427619    
Other Study ID Numbers: 201107741
First Posted: February 9, 2018    Key Record Dates
Results First Posted: October 28, 2021
Last Update Posted: November 23, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphatic Abnormalities
Congenital Abnormalities
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Lymphatic Diseases
Antineoplastic Agents