## Protocol Section
### Identification Module
**NCT ID:** NCT06437158

**Brief Title:** Efficacy and Safety of Different Concentrations of Bleomycin in the Sclerotherapy of Lymphatic Malformations

**Official Title:** Efficacy and Safety of Different Concentrations of Bleomycin in the Sclerotherapy of Lymphatic Malformations

#### Organization Study ID Info
**ID:** 2023-12-19
#### Organization
**Class:** OTHER
**Full Name:** West China Hospital
### Status Module
#### Completion Date
**Date:** 2026-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-25

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-03-08

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-31
**Type:** ESTIMATED
**Study First Submit Date:** 2023-12-19
**Study First Submit QC Date:** 2024-05-25
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** West China Hospital

#### Responsible Party

**Investigator Affiliation:** West China Hospital

**Investigator Full Name:** Yi Ji

**Investigator Title:** Clinical Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Bleomycin has nowadays been more and more widely used in the sclerotherapy of LMs, which has been proven to be primarily dose dependent. We aim to compare the efficacy and safety of different concentrations of Bleomycin in the sclerotherapy of LMs for pediatric patients.

**Detailed Description:** Lymphatic malformations (LMs) are vascular anomalies that arise from abnormal embryonic development of the lymphatic system and might present as dilated lymphatic channels or cysts lined by lymphatic endothelial cells. With an estimated incidence of approximately 1/4000-1/2000, LMs can occur at any site in the lymphatic system, in which head, neck and axilla were mostly detected and have been reported to account for over 75%. Based on the location and size of the lesion and the extent of involvement, LMs may be asymptomatic with incidental detection, or chronic abdominal pain and distension due to their compression of surrounding structures, or critical and even fatal secondary to their volvulus, hemorrhage, infection and rupture. Surgical excision is a definitive treatment for LMs, while it may be difficult at times because of the infiltrative nature of the lesions, leading to a high incidence of complications like vital organ injuries, nerve injuries, bleeding, infection scar formation, and recurrences. Sclerotherapy is a simpler alternative to tedious surgical excision treatment for LMs and avoids the complications related to surgery. As an anticancer drug extracted from Streptomyces verticillus, Bleomycin has been more and more widely used in the sclerotherapy of LMs for pediatric patients, which has been proven to be primarily dose dependent. However, the optimum concentration of Bleomycin in the sclerotherapy of LMs for pediatric patients has not been strictly validated, due to the lack of high-quality RCT studies. We aim to compare the efficacy and safety of different concentrations of Bleomycin in the sclerotherapy of LMs for pediatric patients.

### Conditions Module

**Conditions:**

- Lymphatic Malformation

**Keywords:**

- Lymphatic Malformation

- Bleomycin

- Sclerotherapy

- Intracystic injection

- High-dose concentrations

- Low-dose concentrations

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** We aim to compare the efficacy and safety of different concentrations of Bleomycin in the sclerotherapy of lymphatic malformations for pediatric patients.

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** In this arm, patients with lymphatic malformations were treated by intracapsular injection with low-dose concentrations (1mg/ml) of Bleomycin.

**Intervention Names:**

- Drug: Bleomycin

**Label:** Low-dose Concentrations (1mg/ml) of Bleomycin

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** In this arm, patients with lymphatic malformations were treated by intracapsular injection with high-dose concentrations (2mg/ml) of Bleomycin.

**Intervention Names:**

- Drug: Bleomycin

**Label:** High-dose Concentrations (2mg/ml) of Bleomycin

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- High-dose Concentrations (2mg/ml) of Bleomycin

- Low-dose Concentrations (1mg/ml) of Bleomycin

**Description:** To validated the efficacy and safety of different concentrations of Bleomycin in the sclerotherapy of lymphatic malformations for pediatric patients

**Name:** Bleomycin

**Other Names:**

- Zeocin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Changes of Volume is defined as follows: a complete (90%-100% reduction in LMs volume), substantial (60%-89% reduction in LMs volume), intermediate (20%-59% reduction in LMs volume), or no (\< 20% reduction in LMs volume) response 3 to 6 months post-therapy as assessed by imaging.

**Measure:** Changes of Volume

**Time Frame:** 3 to 6 months post-therapy

#### Secondary Outcomes

**Description:** Score of Pain is selfassessed at each visit on a 0 to 10 visual analog scale (where 0 indicates no pain and 10 indicates the worst pain imaginable), reported along with period duration.

**Measure:** Score of Pain

**Time Frame:** 3 to 6 months post-therapy

**Description:** Global efficacy is assessed at each visit beginning at MS by the physician and self-assessed by the participant and proxy (parents) on a 0 to 10 visual analog scale (where 0 indicates no efficacy and 10 indicates complete resolution).

**Measure:** Global Efficacy

**Time Frame:** 3 to 6 months post-therapy

**Description:** Score of Quality of Life is assessed by the validated Children-Dermatological Life Quality Index (C-DLQI).

**Measure:** Score of Quality of Life

**Time Frame:** 3 to 6 months post-therapy

**Description:** Number of Participants with Efficacy was assessed by 2 independent experts.

**Measure:** Number of Participants with Efficacy

**Time Frame:** 3 to 6 months post-therapy

**Description:** Number of Participants with Safety was assessed based on physical signs and monitoring of imaging examinations or laboratory test.

**Measure:** Number of Participants with Safety

**Time Frame:** 3 to 6 months post-therapy

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Male or female participants less than 14 years of age at the time of informed consent/assent form was signed.
* Participants whose parents have voluntarily given written consent and participants who provided assent (if applicable) after the study has been explained to them.
* Participants with LMs of all sites measured and confirmed via imaging at screening, with rapid progression, resluting in obvious symptoms or dysfunction, which could not be radically resected and could be treated by sclerotherapy.

Exclusion Criteria:

* Penicillin allergy.
* Vascular tumors or combined vascular malformations.
* Participants who may have had surgical or sclerotherapy treatment by other hardeners.
* LMs growing slowly, without obvious symptoms or dysfunction, which does not need to be treated prematurely.

**Maximum Age:** 14 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jijiyuanyuan@163.com

**Name:** Yi Ji, Ph.D.

**Phone:** +8618980606865

**Role:** CONTACT

**Contact 2:**

**Email:** hx2014bsym@163.com

**Name:** Min Yang, M.D.

**Phone:** +8615928411140

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Chengdu

**Contacts:**

***Contact 1:***

- **Email:** jijiyuanyuan@163.com

- **Name:** Yi Ji, Ph.D.

- **Phone:** +8618980606865

- **Role:** CONTACT

***Contact 2:***

- **Email:** hx2014bsym@163.com

- **Name:** Min Yang, M.D.

- **Phone:** +8615928411140

- **Role:** CONTACT

**Country:** China

**Facility:** West China Hospital of Sichuan University

**State:** Sichuan

**Status:** RECRUITING

**Zip:** 610041

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Sun J, Wang C, Li J, Song D, Guo L. The efficacy of bleomycin sclerotherapy in the treatment of lymphatic malformations: a review and meta-analysis. Braz J Otorhinolaryngol. 2023 Jul-Aug;89(4):101285. doi: 10.1016/j.bjorl.2023.101285. Epub 2023 Jun 29.

**PMID:** 37423005

**Citation:** De Maria L, De Sanctis P, Balakrishnan K, Tollefson M, Brinjikji W. Sclerotherapy for lymphatic malformations of head and neck: Systematic review and meta-analysis. J Vasc Surg Venous Lymphat Disord. 2020 Jan;8(1):154-164. doi: 10.1016/j.jvsv.2019.09.007. Epub 2019 Nov 14.

**PMID:** 31734224

**Citation:** Wu Z, Zou Y, Fu R, Jin P, Yuan H. A nomogram for predicting sclerotherapy response for treatment of lymphatic malformations in children. Eur J Med Res. 2022 Oct 21;27(1):209. doi: 10.1186/s40001-022-00844-3.

**PMID:** 36271467

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018190

- Term: Lymphatic Vessel Tumors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000008206

- Term: Lymphatic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12

- Name: Congenital Abnormalities

- Relevance: HIGH

- As Found: Malformations

- ID: M11199

- Name: Lymphangioma

- Relevance: HIGH

- As Found: Lymphatic Malformations

- ID: M25277

- Name: Lymphatic Abnormalities

- Relevance: HIGH

- As Found: Lymphatic Malformations

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3529

- Name: Lymphatic Malformations

- Relevance: HIGH

- As Found: Lymphatic Malformations

### Condition Browse Module - Meshes

- ID: D000008202

- Term: Lymphangioma

- ID: D000044148

- Term: Lymphatic Abnormalities

- ID: D000000013

- Term: Congenital Abnormalities

### Intervention Browse Module - Ancestors

- ID: D000000903

- Term: Antibiotics, Antineoplastic

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M5042

- Name: Bleomycin

- Relevance: HIGH

- As Found: Intravenous injection

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000001761

- Term: Bleomycin

### Misc Info Module

- Version Holder: 2024-05-31
