Classical Hodgkin Lymphoma, Child, Adolescent, Young Adult, Metabolic Response, Survival, Treatment, Brentuximab Vedotin, PET Scan
Conditions
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.
Interventions
DRUGBrentuximab Vedotin for Injection
1.8mg/kg/dose (MAX 180 mg)
RADIATIONresponse-adapted radiation
For patients who did not achieve complete metabolic response at early response assessment based on PET/CT result.
DRUGDoxorubicin
25mg/m2/dose,
DRUGEtoposide
125 mg/m2/dose
DRUGPrednisone
20 mg/m2, BID, orally
DRUGCyclophosphamide
600 mg/m2/dose
DRUGDacarbazine
250 mg/m2/dose; For patients in intermediate/high risk group who did not achieve complete metabolic response at early assessment based on PET/CT results.
3mg/kg/dose; For patients in intermediate/high risk group who did not achieve complete metabolic response at late assessment based on PET/CT results.
DRUGBedamustine
180mg/m2/dose; For patients in intermediate/high risk group who did not achieve complete metabolic response at late assessment based on PET/CT results.
Sponsors
Children's Cancer Group, China
Shanghai Children's Medical Center
Najing Children's Hospital
West China Second University Hospital
Qilu Hospital of Shandong University
Tianjin Medical University Cancer Institute and Hospital
Tongji Hospital
Xiangya Hospital of Central South University
The First Affiliated Hospital of Zhengzhou University
Second Affiliated Hospital of Anhui Medical University
Children's Hospital of Hebei Province
Children's Hospital of Henan Province
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival rate for the entire group and each risk group | 5 years | the overall survival rate for all the patients enrolled |
| 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 |
Countries
China
Contacts
CONTACTYI JIN GAO, MD
CONTACTJIE ZHAO
PRINCIPAL_INVESTIGATORYI JIN GAO, MD
Shanghai Children's Medical Center
Outcome results
None listed