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

Official title

A Phase II/III Study of Brentuximab Vedotin for Newly Diagnosed Classical Hodgkin Lymphoma in Chinese CAYA Based on PET/CT Assessment

Overview

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

• Drug Brentuximab Vedotin for Injection
  1.8mg/kg/dose (MAX 180 mg)
• Radiation response-adapted radiation
  For patients who did not achieve complete metabolic response at early response assessment based on PET/CT result.
• Drug Doxorubicin
  25mg/m2/dose,
• Drug Etoposide
  125 mg/m2/dose
• Drug Prednisone
  20 mg/m2, BID, orally
• Drug Cyclophosphamide
  600 mg/m2/dose
• Drug Dacarbazine
  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.
• Drug Tislelizumab Injection
  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.
• Drug Bedamustine
  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.

Primary outcome measures

• Early complete metabolic response rate for the entire group [Time frame: 5 years]
• Late complete metabolic response rate in intermediate/high risk group [Time frame: 5 years]
• Complete metabolic response rate in intermediate/high risk group after modified Check Mate 744 regimens [Time frame: 5 years]
• Overall survival rate for the entire group and each risk group [Time frame: 5 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Children's Medical Center — Shanghai

Publications

• Huang J, Pang WS, Lok V, Zhang L, Lucero-Prisno DE 3rd, Xu W, Zheng ZJ, Elcarte E, Withers M, Wong MCS; NCD Global Health Research Group, Association of Pacific Rim Universities (APRU). Incidence, mortality, risk factors, and trends for Hodgkin lymphoma: a global data analysis. J Hematol Oncol. 2022 May 11;15(1):57. doi: 10.1186/s13045-022-01281-9. PMID 35546241
• Bao PP, Li K, Wu CX, Huang ZZ, Wang CF, Xiang YM, Peng P, Gong YM, Xiao XM, Zheng Y. [Recent incidences and trends of childhood malignant solid tumors in Shanghai, 2002-2010]. Zhonghua Er Ke Za Zhi. 2013 Apr;51(4):288-94. Chinese. PMID 23927803
• Nie DM, Yuan Q, Yu Y, Wu CJ, Guo X, Zhang AJ, Wang J, Xiao LY, Weng KZ, Fang YJ, Ju XL, Gao J, Xu ZJ, Yang LC, Liu AG, Gao YJ. [A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China]. Zhonghua Er Ke Za Zhi. 2022 Nov 2;60(11):1172-1177. doi: 10.3760/cma.j.cn112140-20220312-00196. Chinese. PMID 36319153
• Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, Cho S, Wu Y, Punnett A, Dave H, Henderson TO, Hoppe BS, Charpentier AM, Keller FG, Kelly KM. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma. N Engl J Med. 2022 Nov 3;387(18):1649-1660. doi: 10.1056/NEJMoa2206660. PMID 36322844
• Metzger ML, Link MP, Billett AL, Flerlage J, Lucas JT Jr, Mandrell BN, Ehrhardt MJ, Bhakta N, Yock TI, Friedmann AM, de Alarcon P, Luna-Fineman S, Larsen E, Kaste SC, Shulkin B, Lu Z, Li C, Hiniker SM, Donaldson SS, Hudson MM, Krasin MJ. Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation. J Clin Oncol. PMID 33826362
• Vardhana S, Cicero K, Velez MJ, Moskowitz CH. Strategies for Recognizing and Managing Immune-Mediated Adverse Events in the Treatment of Hodgkin Lymphoma with Checkpoint Inhibitors. Oncologist. 2019 Jan;24(1):86-95. doi: 10.1634/theoncologist.2018-0045. Epub 2018 Aug 6. PMID 30082490
• Harker-Murray P, Mauz-Korholz C, Leblanc T, Mascarin M, Michel G, Cooper S, Beishuizen A, Leger KJ, Amoroso L, Buffardi S, Rigaud C, Hoppe BS, Lisano J, Francis S, Sacchi M, Cole PD, Drachtman RA, Kelly KM, Daw S. Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults. Blood. 2023 Apr 27;141(17):2075-2084. doi: 10.1182/blo PMID 36564047
• Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov PMID 25311218

Identifiers

NCT: NCT06563245 · CCCG-HL-2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗