Lymphatic MalformationsPhase 2NCT03427619
OK432 (Picibanil) in the Treatment of Lymphatic Malformations
A Phase 2 study testing OK432 in people with Lymphatic Malformations, run by Richard JH Smith at 14 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 6 months to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Lymphatic Malformations
- What is being tested?
- OK432
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 275 participants
- Where
- 14 sitesUnited States
- Study dates
- 5 Oct 2005to 30 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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)
Who cannot join
- 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
Show all 9Show fewer
- 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)
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
The Children's Hospital of Denver
Denver, Colorado, 80218
Spectrum Health-SHMG Ear, Nose, & Throat
Grand Rapids, Michigan, 49546
Children's ENT of Houston
Houston, Texas, 77030
Richard Smith, MD
Iowa City, Iowa, 52242
University of Wisconsin Hospital & Clinic
Madison, Wisconsin, 53279
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals & Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
Vanderbilt University Hospital
Nashville, Tennessee, 37232
Children's Hospital of the Kings Daughter
Norfolk, Virginia, 23507
Oregon Health Sciences University
Portland, Oregon, 97239
Rady Children's Hospital & Health Center San Diego
San Diego, California, 92123
All Children's Hospital
St. Petersburg, Florida, 33701
SUNY Health Science Center
Syracuse, New York, 13210
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 2, Multicenter, Open Label Study to Evaluate the Efficacy and Safety of OK-432 Immunotherapy in Individuals With Lymphatic Malformations
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.
Read the 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.
- Conditions
- Lymphatic Malformations
- Being tested
- OK432
- Medical subject headings
- Lymphatic Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OK432Drug
Also called Picibanil
OK432 will be injected at dosage of 0.01 to 0.05 mg/mL 6-12 weeks apart up to 4 injections total.
| Study group | Role | What they receive |
|---|---|---|
| OK432 (Picibanil) | Experimental | 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. Receives: Drug: OK432 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 to 6 Months Post-Therapy
Secondary outcomes (3)
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
Measured: 1 to 6 Months Post-Therapy
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.
Measured: 1 to 6 Months Post-Therapy
Change From Baseline in Lesion Volume
Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.
Measured: Baseline and 1 to 6 Months Post-Therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2018
- Study start5 Oct 2005
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphatic MalformationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All eligible participants receive the actual drug.
- Masking
- None (open label)
- Enrolment
- 275 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard JH Smith
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Richard JH Smith, University of Iowa
- Investigators
- Richard JH Smith, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03427619
- Sponsor's protocol ID
- 201107741
- Status last verified
- Oct 2021
- First submitted
- 10 Jan 2018
- Last updated
- 23 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Open Label Study to Evaluate the Efficacy and Safety of OK-432 Immunotherapy in Individuals With Lymphatic Malformations
- ClinicalTrials.gov ID
- NCT03427619
- Acronym / sponsor ID
- 201107741
- Conditions
- Lymphatic Malformations
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 275 participants (actual)
- Lead sponsor
- Richard JH SmithUniversity, hospital or other
- Study start
- 5 Oct 2005 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 9 Feb 2018 (actual)
- Results
- Posted 28 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All eligible participants receive the actual drug.
| Arm | Type | Receives |
|---|---|---|
| OK432 (Picibanil) | Experimental | Drug: OK432There 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. |
Who may qualify
- Ages
- 6 months to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OK432Also: PicibanilOK432 will be injected at dosage of 0.01 to 0.05 mg/mL 6-12 weeks apart up to 4 injections total. | Drug | OK432 (Picibanil) |
Primary outcome
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
3 secondary outcomes
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 With Investigator-Evaluated Overall Response
Time frame: 1 to 6 Months Post-Therapy
Change From Baseline in Lesion Volume
Time frame: Baseline and 1 to 6 Months Post-Therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard JH Smith, MD principal investigator
University of Iowa
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OK432 in people with Lymphatic Malformations, run by Richard JH Smith at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.