Brentuximab Vedotin for Newly Diagnosed CHL in Chinese CAYA Based on PET/CT Assessment

Phase 2

Recruiting

• Conditions: Brentuximab Vedotin; Young Adult; PET Scan; Classical Hodgkin Lymphoma; Treatment; Child; Adolescent; Metabolic Response; Survival
• Interventions: Drug: Brentuximab Vedotin for Injection; Radiation: response-adapted radiation; Drug: Doxorubicin; Drug: Etoposide; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Dacarbazine; Drug: Tislelizumab Injection; Drug: Bedamustine

• Registration Number: NCT06563245
• Lead Sponsor: Children's Cancer Group, China

Brief Summary

Generally, pediatric patients tolerate acute toxicities but are vulnerable to late effects. Thus, increasing chemotherapy intensity to achieve more rapid complete early response to limit radiation therapy is worth testing. In this CCCG-HL-2024 study, Brentuximab vedotin (Bv) was used to replace VCR and bleomycin in the ABVE-PC regimen in the previous CCCG-HD-2018 study, respectively, to form a Bv-AEPC regimen for the treatment of newly diagnosed classic Hodgkin lymphoma (cHL) in children, adolescents and young adults. On the premise of maintaining a 4-year event free survival (EFS)\>90% in the low-, intermediate-and high-risk groups, increase the early assessment complete response rate (the overall early complete response rate increased by 20%, that is, from 54.0% to 74.0%) to further reduce the proportion of children receiving radiotherapy to benefit them.

Detailed Description

In this CCCG-HL-2024 study, Brentuximab vedotin (Bv) was used to replace VCR and bleomycin in the ABVE-PC regimen in the previous CCCG-HD-2018 study, respectively, to form a Bv-AEPC regimen for the treatment of newly diagnosed classic Hodgkin lymphoma (cHL) in children, adolescents and young adults. Bv is currently the most widely used "new drug" in childhood cHL.

For patients in the intermediate/high-risk group who did not achieve metabolic complete remission rate (CMR) at the early assessment based on PET/CT results, an intensive regimen of Bv-Dac-APC (Bv-APC plus dacarbazine) was applied for 2 or 3 courses to further improve event-free survival without increasing long-term reproductive toxicity.

For patients in the intermediate/high-risk group who did not achieve CMR after the Bv-Dac-AEPC regimen, a modified Check Mate 744 regimen (PD-1 monoclonal antibody, Bv,+/-bedamostine, autologous stem cell transplantation/radiotherapy) was applied to improve the CMR of patients before irradiation, hoping to reduce the primary treatment failure rate to almost zero.

Study Timeline

• Study First Submitted: 2024-08-18
• Study First Submitted QC: 2024-08-18
• Study First Posted: 2024-08-20
• Study Start: 2024-09-25
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Primary Completion: 2029-11-15
• Study Completion: 2039-11-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

• Ages >=2~<35 years at the time of enrollment;
• Patients with newly diagnosed, pathologically confirmed classical Hodgkin lymphoma (HL) by at least 2 tertiary referral centers for pathology;
• Adequate organ function;
• Patients and/or their parents or legal guardians sign a written informed consent;

Exclusion Criteria

• Patients with nodular lymphocyte-predominant HL;
• Patients with an immunodeficiency that existed prior to diagnosis; such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible;Patients known to be positive for HIV are not eligible.
• Patients who are pregnant; Lactating females who plan to breastfeed.
• Patients who received systemic corticosteroids within 28 days of enrollment on this protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High risk group	Tislelizumab Injection	Stage IIB Stage IIIB Stage IV
Low risk group	Etoposide	Stage IA , no bulky Stage IIA, no bulky
Intermediate risk group	Brentuximab Vedotin for Injection	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
High risk group	response-adapted radiation	Stage IIB Stage IIIB Stage IV
Low risk group	Brentuximab Vedotin for Injection	Stage IA , no bulky Stage IIA, no bulky
Low risk group	Doxorubicin	Stage IA , no bulky Stage IIA, no bulky
Intermediate risk group	response-adapted radiation	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
High risk group	Etoposide	Stage IIB Stage IIIB Stage IV
Low risk group	response-adapted radiation	Stage IA , no bulky Stage IIA, no bulky
Intermediate risk group	Tislelizumab Injection	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
Intermediate risk group	Bedamustine	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
High risk group	Brentuximab Vedotin for Injection	Stage IIB Stage IIIB Stage IV
High risk group	Bedamustine	Stage IIB Stage IIIB Stage IV
Low risk group	Cyclophosphamide	Stage IA , no bulky Stage IIA, no bulky
Low risk group	Prednisone	Stage IA , no bulky Stage IIA, no bulky
Intermediate risk group	Prednisone	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
Intermediate risk group	Etoposide	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
Intermediate risk group	Doxorubicin	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
Intermediate risk group	Cyclophosphamide	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
Intermediate risk group	Dacarbazine	Stage IA, with bulky Stage IIA, with bulky Stage IB, with/without bulky Stage IAE, with/without bulky Stage IIAE, with/without bulky Stage IIIA, with/without bulky
High risk group	Doxorubicin	Stage IIB Stage IIIB Stage IV
High risk group	Dacarbazine	Stage IIB Stage IIIB Stage IV
High risk group	Prednisone	Stage IIB Stage IIIB Stage IV
High risk group	Cyclophosphamide	Stage IIB Stage IIIB Stage IV

Primary Outcome Measures

Name	Time	Method
Early complete metabolic response rate for the entire group	5 years	Early complete metabolic response rate after 2 cycle of Bv-AEPC based on PET/CT result for the entire group
Late complete metabolic response rate in intermediate/high risk group	5 years	Late complete metabolic response rate based on PET/CT results for patients who did not achieve early complete metabolic response after 2 or 3 cycles of Bv-Dac-AEPC
Complete metabolic response rate in intermediate/high risk group after modified Check Mate 744 regimens	5 years	Complete metabolic response rate based on PET/CT results for patients who receive a modified Check Mate 744 regimen
Overall survival rate for the entire group and each risk group	5 years	the overall survival rate for all the patients enrolled

Trial Locations

Locations (1)

Shanghai Children's Medical Center; 🇨🇳 Shanghai, China