Diseases and Abnormalities at or Before Birth

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Congenital Abnormalities

Lymphangioma

Lymphatic Abnormalities

Neoplasms by Histologic Type

Lymphatic Diseases

Lymphatic Malformations

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

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.

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

OK432

Richard JH Smith, MD

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.

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.

All eligible participants receive the actual drug.

OK432 (Picibanil) in the Treatment of Lymphatic Malformations

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

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

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

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.

Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.

Richard JH Smith

Principal Investigator

In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug.

Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)

OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin.

OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart

OK-432

Demographic information for age was available for 273 subjects. Missing for 2 subjects.

Age, Continuous

Demographic information for gender was available for 274 subjects. Missing for 1 subject.

Sex: Female, Male

Hispanic or Latino

American Indian or Alaska Native

White

Black or African American

Asian

Other

Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.

Race/Ethnicity, Customized

United States

Region of Enrollment

The Safety Population included all enrolled subjects that have been treated with at least one injection of OK-432. Results were based on a retrospective analysis of source-verified data and only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses.

Results are based on a retrospective analysis of source-verified data that include subjects enrolled in the open label study. This study was conducted to provide patients with continued access to OK-432 on a compassionate use basis. Response data were not well documented for everyone. Subjects with missing data included those who were lost to follow up, had incomplete or missing CRFs or imaging studies.

Dr. Richard Smith

The modified Intent to Treat (mITT) Population includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The efficacy data were presented as observed for subjects with non-missing data in the mITT Population (N = 78).

Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging

Number of subjects who achieved a complete response

Number of subjects who achieved a substantial response

Number of subjects who achieved an intermediate response

Number of subjects who achieved no response

The mITT includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The efficacy data were presented as observed for subjects with non-missing data in the mITT Population (N = 78).

Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging

The mITT Population includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The investigator assessed response data were presented as observed for subjects with non-missing data in the mITT Population (N = 98).

Number of Participants With Investigator-Evaluated Overall Response

The mITT includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The efficacy data were presented as observed for subjects with non-missing data in the mITT Population (N = 76).

Change From Baseline in Lesion Volume

Overall Study

Hemangioma

Neoplasms, Vascular Tissue

Determine protocols for treatment of airway vascular malformation and to evaluate results from treatment of these lesions.

Protocols for Treatment

Gresham T Richter, M.D.

Jessica L Boswell, BS, CRS

Controversy exists in the treatment of airway hemangiomas ranging from tracheotomy, various lasers, to open removal, none of which have proven to be a gold standard. Venous malformations of the airway are difficult to treat and also require laser therapy or open removal and often repeated treatments are required. Similarly airway lymphatic malformations can require multiple treatment modalities as well as multiple procedures and are infrequently eradicated when extensive. New uses for various lasers and differing treatment protocols are frequently developed. Review of the treatment modalities and efficacy of these methods is required. The goal of this research is to determine protocols for treatment of airway vascular malformation and to evaluate our results from treatment of these lesions.

Airway Vascular Lesions

University of Arkansas

Micronutrients

Selenium

Antioxidants

Protective Agents

Trace Elements

Michael E Kelly, MD, PhD

The investigators propose a pilot trial to obtain preliminary information regarding the safety and response rate of patients with symptomatic lymphatic malformations treated with oral Selenium. Information obtained in this pilot trial will be used to plan future phase 2 clinical trials.

Hypotheses:

* Selenium will be safe and efficacious in the treatment of adolescents and young adults with symptomatic lymphatic malformations
* Disease response will correlate with serum levels of selenium and blood levels of antioxidants essential to selenium metabolism.

Selenium in the Treatment of Complicated Lymphatic Malformations

Pilot Clinical Trial to Estimate the Safety and Efficacy of Selenium in the Treatment of Complicated Lymphatic Malformations in Adolescents and Young Adults

Disease will be assessed by volumetric MRI and patient quality of life assessments at 6 months of therapy and compared to pretreatment values.

Whole blood will be drawn prior to therapy and at specific time intervals after initiating selenium. Serum concentrations of selenium, selenium-dependent tripeptide glutathione and IL-20 will be measured and correlated with outcome

Medical College of Wisconsin

Cystic Hygroma

Up to .2 mg per injection, given intralesionally every 6-8 weeks

picibanil

Richard J Smith

OBJECTIVES:

I. Determine the efficacy of picibanil sclerotherapy in children with macrocystic lymphangioma.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to prior treatment (no prior treatment vs prior surgical treatment) and geographic area.

Patients who meet all study criteria are put in the "Immediate Treatment Group." Patients receive an intralesional injection of picibanil (OK432) with the aid of ultrasonography or transillumination for localization of cysts. Treatment repeats every 6-8 weeks for a total of up to 4 injections.

After completion of treatment, patients are followed at 6 months, 1 year, and 2 years.

Completion date provided represents the completion date of the grant per OOPD records

Study of Picibanil (OK432) Sclerotherapy in Children With Macrocystic Lymphatic Malformations

Treatment of Cystic Hygroma (Lymphangiomas) in Children- Picibanil(OK432) Sclerotherapy-Multicenter Trial

University of Iowa

Heart and Blood Diseases

Arteriovenous Malformations

Vascular Malformations

Cardiovascular Abnormalities

Vascular Diseases

Gal Shafirstein, Ph.D.

Jessica L Boswell

To develop a non-invasive, simple and affordable, measurement technique to differentiate hemangiomas from subtypes of VMS. The purpose of this study is to determine the best office based diagnositc instrument for differentiating the subtype of vascular lesions. The instrument must be simple and affordable so it can be used by primary car physicians in the doctor office. The procedure will be based on non-invasive and unharmful measurements that will be compared to the diagnosis from specialized physicians in this field and the final pathology.

Diagnosis of Hemangiomas and Vascular Malformations

Diagnosis of Hemangiomas and Vascular Malformations Using Non-invasive Imaging Devices

Vasodilator Agents

Urological Agents

Anticoagulants

Other Dietary Supplements

Sildenafil Citrate

Citric Acid

Sodium Citrate

Phosphodiesterase 5 Inhibitors

Phosphodiesterase Inhibitors

Enzyme Inhibitors

Citrate

Placebo Drug: Placebo tablets (resembling Revatio)

Active Drug: Sildenafil tablets (Revatio)

Sildenafil 20 mg tablets

Placebo tablets (resembling Revatio)

Joyce Teng, MD, PhD

A Phase 2 study to evaluate safety and efficacy of sildenafil taken orally to improve or resolve lymphatic malformations in children. Subjects may receive either placebo or treatment in an oral dosage with an open label extension for subjects who received placebo. The study treatment assignment will be randomized in a double blind fashion. MRI examination will evaluate change in lesion volume due to treatment. Other safety and efficacy measures will be taken through the 32-week study duration.

Funding Source - FDA OOPD

Lymphatic malformations (LMs) are localized areas of abnormal development of the lymphatic system that commonly occur in the head and neck of children. LMs are considered a rare or orphan disease which causes complications including pain, ulceration, secondary infection, infiltration of other organs, and death. Current therapies involve surgical excision or methods of chemical or physical destruction of portions of lesions. No therapies are uniformly effective and all have the risk of significant adverse events. We recently witnessed almost complete resolution of a LM lesion in a child who was treated with sildenafil oral therapy for pulmonary arterial hypertension. We have subsequently evaluated additional subjects who improved with sildenafil. The goal of this clinical research trial is to document the benefit or absence of benefit of sildenafil therapy for LMs and identify which type of patient will benefit from sildenafil. This study is a double-blind placebo-controlled trial which involves precise documentation of volume changes associated with therapy or placebo by using MRI segmentation techniques. We will also observe and document the clinical response to sildenafil or placebo using clinical evaluation scores and surveys. The results of the study should identify characteristics of LM lesions which may suggest a beneficial response to sildenafil therapy. Sildenafil has very low risk of side effects in the dosage used in this trial. Documentation of an effective response of LMs to sildenafil will accelerate the interest in, and the ability to understand, the mechanisms of LM formation and treatment.

Sildenafil for the Treatment of Lymphatic Malformations

Phase 2 Study of Sildenafil for the Treatment of Lymphatic Malformations

The IPD will only be shared de-identified to our study staff and human subjects approved subsites. These results will eventually be published, but will be completed around 2022.

Participants will be followed for the duration of the study, an expected average of 20 weeks.

Subject's evaluation of the overall change in lymphatic malformation. Participants will be followed from baseline to 20 weeks.

Patients rated change as no improvement, minimal improvement (1-25% change), fair improvement (25-50% change), good improvement (50-75% change), and excellent improvement (75-100% change).

Ann & Robert H Lurie Children's Hospital of Chicago

Stanford University

Placebo (resembling Revatio) for 20 weeks.

Double-Blind Placebo

Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg).

Open-Label Sildenafil

Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg).

Double-Blind Sildenafil

Placebo (resembling Revatio) for 20 weeks. Participants randomized to placebo had the option to enter a 20-week open-label phase to receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.

Double-Blind Placebo Then Open-Label Sildenafil

Sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12-week follow-up period.

Total

Age, Categorical

Ethnicity data are available for only 6 participants in the placebo group.

Ethnicity (NIH/OMB)

African American

Indian

More than one race

Unknown/Not reported

Race data are available for only 6 participants in the placebo group.

Baseline lesion volume data are available for only 6 participants in the placebo group.

Lesion volume

Only 1 of 4 planned sites participated in this trial; the study did not meet its planned enrollment and the results are underpowered.

Jean Teng, MD, PhD

Placebo (resembling Revatio) for 20 weeks, followed by a 12 week follow-up period.

Participants who complete placebo then receive active sildenafil (Revatio) for 20 weeks three times daily (weight-based: 10 mg TID for participants weighing 8-20 kg; 20 mg TID for participants weighing \>20 kg), followed by a 12 week follow-up period.

Double-blind Sildenafil

Participants who completed each treatment period are included in the analysis

Change in Lesion Volume of the Test Medication as Evaluated by MRI Examination.

No improvement

Minimal improvement

Fair improvement

Good improvement

Excellent improvement

Participants with data at both baseline and week 20 are included in the analysis

Change in Subject's Assessment of Change in Lymphatic Malformation Overall Score

Randomized Phase (20 Weeks)

Open-label Phase (20 Weeks)

Follow-up Period (12 Weeks)

Microcystic Lymphatic Malformation

Adult participants (≥18 years of age) who will receive dose 1 of alpelisib an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)

Adult participants (≥18 years of age) who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).

Pediatric participants 6-17 years of age who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)

Pediatric participants 6-17 years of age who will receive dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).

Adult participants (≥18 years of age) who will receive alpelisib at the dose selected for confirmatory phase in adult participants (Stage 2)

Adult participants (≥18 years of age) who will receive matching placebo

Pediatric participants (6-17 years of age) who will receive alpelisib at the dose selected for confirmatory phase in pediatric participants (Stage 2)

Pediatric participants (6-17 years of age) who will receive matching placebo

Pediatric participants of 2-5 years who will dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier

In Stage 1: adult participants (≥18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will recieve dose 2 or dose 3 of alpelisib.

In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 2-5 years of age will receive dose 3 of alpelisib

Alpelisib

In Stage 2, participants will receive matching placebo for 24 weeks of the study

Placebo

Novartis Pharmaceuticals

Joyce Teng

Katie Schultz

Bryan Sisk

The main purpose of this study in participants with PIK3CA-mutated lymphatic malformations (LyM) is to assess the change in radiological response and symptom severity upon treatment with alpelisib as compared to placebo.

This is a phase II/III multi-center study with two stages:

* Stage 1 is designed to select the dose(s) for the confirmatory phase (DSCP) for alpelisib in Stage 2 and will comprise a 24-week open-label core phase in adult (≥18 years of age) and pediatric participants (6-17 years of age) with PIK3CA-mutated LyM, followed by an extension. After eligibility has been confirmed at screening, participants will be randomized to the different alpelisib doses according to their age. Depending on the results at the end of Stage 1 core phase, the Stage 2 will be opened to adult and/or pediatric participants or the study may be stopped.
* Stage 2 is designed to confirm the efficacy and assess safety of alpelisib at the DSCP in participants with PIK3CA-mutated LyM and will comprise a 24-week randomized, double blind, placebo-controlled confirmatory phase in adult (≥18 years of age) and pediatric participants 6-17 years of age followed by an open-label extension. After eligibility has been confirmed at screening participants will be randomized to alpelisib or placebo.

Additionally, in parallel, Stage 2 will include a 24-week open-label core phase in pediatric participants 2-5 years of age followed by an extension, if pediatric participants will be enrolling in Stage 2.

Based on the results of the 24-week open-label core phase of Stage 1, the dose(s) for Stage 2 will be selected by Novartis in consultation with the Steering Committee (SC). During the 24-week randomized, double blind, placebo-controlled core phase of Stage 2, an Independent Data Monitoring Committee (DMC) will conduct periodic safety reviews.

Stage 1 is open label. For adult and pediatric participants 6-17 years of age, Stage 2 comprises a 24-week double-blind period followed by an open-label period. For pediatric participants 2-5 years of age, Stage 2 is open label.

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

A Two-stage Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions. The percentage of participants with a radiological response at Week 24 of Stage 2 in adult and pediatric (6-17 years of age) groups will be assessed

PGI-S is a single item measure to assess the overall severity of a patient's condition. This single item instrument uses a 5-point rating scale, which ranges from 1 (no symptoms) to 5 (very severe). Lower scores indicate better health status. The percentage of participants with at least a 1-point improvement compared to baseline at Week 24 of Stage 2 in adult and pediatric (6-17 years of age) groups will be assessed

Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions. The percentage of participants with a radiological response at Week 24 of Stage 2 in pediatric participants 2-5 years of age will be assessed

PGI-C is a single item measure to assess the change in overall symptoms severity since the start of study. This single item instrument uses a 7-point rating scale, which ranges from 1 (very much improved) to 7 (very much worse). Lower scores indicate better health status. The change from baseline in PGI-C score will be assessed in adult and pediatric (6-17 years of age) participants

The PROMIS-29 plus 2 Profile v2.1 (completed by adult participant) includes 29 items across domains of depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, ability to participant in social roles and activities, cognitive function abilities and pain intensity..

The PROMIS Pediatric-25 Profile v2.0 (completed by children over 8 years of age) and PROMIS Parent-Proxy-25 Profile v2.0 (completed by parents for children under 8 years of age) include 25 items across the domains of depressive symptoms, anxiety, physical function-mobility, pain interference, fatigue, and peer relationships and pain intensity All items (except the pain intensity item) use a 5-point Likert scale, which ranges from 1 (not at all) to 5 (very much). The pain internsity item is scored on a 0-10 numeric rating scale, where 0 represents "no pain" and 10 represents "worst imaginable pain".

The change from baseline in PROMIS domains will be assessed

The IGIC involves a single question that asks the investigator to rate the change in the patient's condition since the start of treatment or intervention, using a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse). The change from baseline in IGIC score will be assessed in adult and pediatric (6-17 years of age) participants

The EQ-5D-5L (completed by adult participants) includes 5 items addressing dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 response options, ranging from 1=no problems to 5=extreme problems The EQ-5D-Y (completed by children over 8 years of age) and EQ-5D-Y Proxy version (completed by parent for participants under 8 years of age or unable to record for themselves) includes 5 items addressing dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 3 response options, ranging from 1= no problems to 3= a lot of problems

DOR is defined as the time from first documented response until progression of LyM lesions by BIRC or death. This analysis only applies to participants who are on treatment with alpelisib (Stage 1 and 2) and who achieve response.

Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.

The percentage of participants (adult and pediatric 6-17 years of age) with radiological response at Week 24 of Stage 1 will be assessed.

Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.

The percentage of participants who receive alpelisib (Stage 1 and 2) with radiological response will be assessed.

Alpelisib plasma concentrations in adult and pediatric participants (Stage 1 and 2).

Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 (Stage 1 and 2)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
OK432 (Picibanil) in the Treatment of Lymphatic Malformations	NCT03427619	Lymphatic Malfo...	OK432	6 Months - 17 Years	University of Iowa
Airway Vascular Lesions	NCT00866827	Hemangiomas Venous Malforma... Lymphatic Malfo...	Protocols for T...	-	University of Arkansas
Selenium in the Treatment of Complicated Lymphatic Malformations	NCT01212965	Lymphatic Malfo...	Selenium	14 Years - 30 Years	Medical College of Wisconsin
Study of Picibanil (OK432) Sclerotherapy in Children With Macrocystic Lymphatic Malformations	NCT00010452	Lymphatic Malfo...	picibanil	6 Months - 18 Years	FDA Office of Orphan Products Development
Diagnosis of Hemangiomas and Vascular Malformations	NCT00577213	Hemangiomas Vascular Malfor... Venular Malform... Venous Malforma... Lymphatic Malfo... Arteriovenous M...		- 75 Years	University of Arkansas
Sildenafil for the Treatment of Lymphatic Malformations	NCT02335242	Lymphatic Malfo... Lymphatic Disea...	Sildenafil 20 m... Placebo tablets...	6 Months - 10 Years	Stanford University
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.	NCT05948943	Lymphatic Malfo...	Alpelisib Placebo	2 Years -	Novartis
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.	NCT05948943	Lymphatic Malfo...	Alpelisib Placebo	2 Years -	Novartis

Spots Global Cancer Trial Database for lymphatic malformations