Low- vs High-Dose Sirolimus With Prednisolone for KHE and KMP

NCT07656909 | Recruiting Phase 2 DMC

• 1 other identifier: RCT20260615
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized clinical trial evaluates if low-dose sirolimus (target trough 4-8 ng/mL) combined with prednisolone is noninferior in efficacy but superior in safety compared to standard high-dose sirolimus (target trough 10-15 ng/mL) combined with prednisolone in pediatric patients with kaposiform hemangioendothelioma and Kasabach-Merritt phenomenon (KHE with KMP), with participants randomized 1:1 to receive the assigned regimen, undergo routine blood and imaging monitoring, and be evaluated for clinical response and adverse events.

Conditions

Kaposiform Hemangioendothelioma (KHE); Kasabach Merritt Phenomenon

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving Platelet Count Recovery

  The proportion of participants who achieve platelet count recovery, defined as a platelet count ≥100 × 10⁹/L without platelet transfusion support, during the study period.

  2 months

Secondary Outcomes (6)

• Proportion of Participants Achieving Fibrinogen Recovery

  2 months

• Change in D-Dimer Level From Baseline

  2 months

• Change in KHE Tumor Volume From Baseline

  6 and 12 months

• The changes in the patient's symptoms and/or complications.

  6 and 12 months

• Frequency of adverse events

  12 months

Study Arms (2)

Low-Dose Sirolimus Plus Prednisolone

EXPERIMENTAL

Participants receive oral sirolimus with dose adjustments to maintain a target plasma trough concentration of 4-8 ng/mL, in combination with prednisolone, for a treatment duration of 12 months.

Drug: Sirolimus (RAPAMUNE)

High-Dose Sirolimus Plus Prednisolone

ACTIVE COMPARATOR

Participants receive oral sirolimus with dose adjustments to maintain a target plasma trough concentration of 10-15 ng/mL, in combination with prednisolone, for a treatment duration of 12 months.

Drug: Sirolimus (RAPAMUNE)

Interventions

Sirolimus (RAPAMUNE) DRUG

Participants will receive oral sirolimus in combination with prednisolone. Patients will be randomized in a 1:1 ratio to either a low-dose sirolimus group, with dose adjustments to maintain a target plasma trough concentration of 4-8 ng/mL, or a high-dose sirolimus group, with dose adjustments to maintain a target plasma trough concentration of 10-15 ng/mL. Prednisolone will be administered according to the study protocol and tapered based on clinical response. The total treatment duration will be 12 months.

High-Dose Sirolimus Plus Prednisolone; Low-Dose Sirolimus Plus Prednisolone

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Presenting a KHE with the following characteristics:
• Clinical features and histological findings consistent with progressive, non-resectable KHE associated with KMP.
• Patients must be 0 - 18 years of age at the time of study entry.
• Without functional impairment requiring treatment of corticosteroid.
• Organ function requirements:
• Adequate liver function:
• Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and
• ALT and AST less than or equal to 2.5 x upper limit normal (ULN) for age.
• Adequate renal function:
• years of age maximum serum creatinine (mg/dL) of 0.8
• years of age maximum serum creatinine (mg/dL) of 1.0
• years of age maximum serum creatinine (mg/dL) of 1.2
• years of age maximum serum creatinine (mg/dL) of 1.5
• Adequate bone marrow function: Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 to the ninth/Liter.
• Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.

You may not qualify if:

• Allergy to sirolimus or other rapamycin analogues.
• Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization.
• Patients must not be known to be Human Immunodeficiency Virus positive or known immunodeficiency. Testing is not required unless a condition is suspected.
• Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
• Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
• Patients who have a history of malignancy.
• Patients with an inability to participate or to follow the study treatment and assessment plan.

Sponsors & Collaborators

• Yi Ji: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (13)

• Lauven PM, Schwilden H, Stoeckel H. Threshold hypnotic concentration of methohexitone. Eur J Clin Pharmacol. 1987;33(3):261-5. doi: 10.1007/BF00637559.

  PMID: 3691614 RESULT

• Ji Y, Chen S, Yang K, Zhou J, Zhang X, Jiang X, Xu X, Lu G, Qiu L, Kong F, Zhang Y. A prospective multicenter study of sirolimus for complicated vascular anomalies. J Vasc Surg. 2021 Nov;74(5):1673-1681.e3. doi: 10.1016/j.jvs.2021.04.071. Epub 2021 May 31.

  PMID: 34082006 RESULT

• Wada Y, Iijima K, Yonezawa T. [The effects of nitroglycerin induced hypotension on the tissue blood flow in dogs under halothane anesthesia]. Masui. 1985 Sep;34(9):1208-15. No abstract available. Japanese.

  PMID: 3936944 RESULT

• Zhou J, Yang K, Dai S, Qiu T, Zhang X, Gong X, Chen S, Ji Y. Clinical features and management of kaposiform hemangioendothelioma and tufted angioma: Similarities and differences. J Am Acad Dermatol. 2022 Jul;87(1):172-174. doi: 10.1016/j.jaad.2021.07.012. Epub 2021 Jul 14. No abstract available.

  PMID: 34273457 RESULT

• Zhou J, Qiu T, Zhang Z, Lan Y, Huo R, Xiang B, Chen S, Qiu L, Xia C, Xu X, Li J, Ma Y, Yao W, Wang Z, Dong C, Qin Z, Tai M, Guo L, He X, Gu S, Li L, Hou F, Cai Y, Wang H, Wang J, Jiang X, Zheng J, Li K, Ji Y. Consensus statement for the diagnosis, treatment, and prognosis of kaposiform hemangioendothelioma. Int J Cancer. 2025 May 15;156(10):1986-1994. doi: 10.1002/ijc.35344. Epub 2025 Jan 20.

  PMID: 39831682 RESULT

• Zhou J, Lan Y, Qiu T, Zhang Z, Gong X, Zhang X, Yang C, Zhou Z, Zhang Y, Yang M, Fu J, He C, Peng Q, Hu F, Xia C, Kong F, Chen S, Ji Y. Efficacy and safety of high-vs low-dose sirolimus in patients with kaposiform hemangioendothelioma: A randomized clinical trial. J Am Acad Dermatol. 2025 Jul;93(1):124-131. doi: 10.1016/j.jaad.2025.03.023. Epub 2025 Mar 17.

  PMID: 40107509 RESULT

• Zhou J, Ji Y. Kaposiform hemangioendothelioma. J Am Acad Dermatol. 2026 Mar 12:S0190-9622(26)00396-8. doi: 10.1016/j.jaad.2026.03.020. Online ahead of print. No abstract available.

  PMID: 41831614 RESULT

• Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood. 2022 Mar 17;139(11):1619-1630. doi: 10.1182/blood.2021014027.

  PMID: 35030255 RESULT

• Rossler J, Baselga E, Davila V, Celis V, Diociaiuti A, El Hachem M, Mestre S, Haeberli D, Prokop A, Hanke C, Loichinger W, Quere I, Baumgartner I, Niemeyer CM, Kapp FG. Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13.

  PMID: 33580918 RESULT

• Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB, Trenor CC 3rd. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. J Pediatr. 2013 Jan;162(1):142-7. doi: 10.1016/j.jpeds.2012.06.044. Epub 2012 Aug 4.

  PMID: 22871490 RESULT

• Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.

  PMID: 28486787 RESULT

• Wang Z, Yao W, Sun H, Dong K, Ma Y, Chen L, Zheng S, Li K. Sirolimus therapy for kaposiform hemangioendothelioma with long-term follow-up. J Dermatol. 2019 Nov;46(11):956-961. doi: 10.1111/1346-8138.15076. Epub 2019 Sep 5.

  PMID: 31489702 RESULT

• Ji Y, Chen S, Yang K, Xia C, Li L. Kaposiform hemangioendothelioma: current knowledge and future perspectives. Orphanet J Rare Dis. 2020 Feb 3;15(1):39. doi: 10.1186/s13023-020-1320-1.

  PMID: 32014025 RESULT

MeSH Terms

Conditions

Kaposiform Hemangioendothelioma; Kasabach-Merritt Syndrome

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Yi Ji

  West China Hospital

  STUDY CHAIR

• Jiangyuan Zhou, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Ji, PhD

CONTACT

02885423453; jijiyuanyuan@163.com

Jiangyuan Zhou, MD

CONTACT

13668491160@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 18, 2026
• Study Start: June 16, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 18, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)