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Phase 1 study of bendamustine in combination with clofarabine, etoposide, and dexamethasone in pediatric patients with relapsed or refractory hematologic malignancies.
Jeha, Sima; Crews, Kristine R; Pei, Deqing; Peyton, Melissa; Panetta, John C; Ribeiro, Raul C; Zhao, Xujie; Campbell, Patrick; Metzger, Monika L; Yang, Jun J; Cheng, Cheng; Pui, Ching-Hon; Bhojwani, Deepa.
Afiliação
  • Jeha S; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Crews KR; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Pei D; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Peyton M; Cancer Center Administration, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Panetta JC; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Ribeiro RC; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Zhao X; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Campbell P; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Metzger ML; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Yang JJ; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Cheng C; Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Pui CH; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Bhojwani D; Children's Hospital Los Angeles, Los Angeles, California.
Cancer ; 127(12): 2074-2082, 2021 06 15.
Article em En | MEDLINE | ID: mdl-33598942
BACKGROUND: A phase 1 study was conducted to determine the maximum tolerated dose of bendamustine when given in combination with clofarabine, etoposide, and dexamethasone daily for 5 days in children and adolescents with relapsed or refractory hematologic malignancies. METHODS: Patients younger than 22 years with second or greater relapsed or refractory acute leukemia or lymphoma after 2 or more prior regimens were eligible. With the rolling 6 design, participants received escalating doses of bendamustine (30, 40, or 60 mg/m2 /d) in combination with clofarabine (40 mg/m2 ), etoposide (100 mg/m2 ), and dexamethasone (8 mg/m2 ) daily for 5 days. Optional pharmacokinetic studies were performed in cycle 1 on day 1 and day 5. RESULTS: Sixteen patients were enrolled. Six patients were treated at the dose level of 30 mg/m2 /d, 6 were treated at the dose level of 40 mg/m2 /d, and 4 were treated at the dose level of 60 mg/m2 /d. The dose-limiting toxicity was prolonged myelosuppression. The combination was otherwise well tolerated. The recommended dose of bendamustine in this combination was 30 mg/m2 /d for 5 days. Ten responses were observed after 1 cycle: 6 complete remissions, 1 durable minimal residual disease-negative complete remission without platelet recovery in a patient with early T-cell precursor leukemia, and 3 partial remissions. Six patients proceeded to transplantation. The event-free survival rate was 40.6% (95% confidence interval [CI], 17.5%-63.7%) at 1 year and 33.9% (95% CI, 11.9%-55.9%) at 3 years. CONCLUSIONS: Bendamustine is well tolerated in combination with clofarabine, etoposide, and dexamethasone. The combination administered over 5 days is effective for multiple relapsed and refractory hematologic malignancies. This trial is registered with ClinicalTrials.gov (NCT01900509). LAY SUMMARY: Improvements to the existing chemotherapy regimen are still needed for patients who relapse after targeted therapies and immunotherapies and for those who are not eligible for or have no access to such therapies. A regimen combining cyclophosphamide, clofarabine, and etoposide has been used in relapsed and refractory pediatric patients with hematologic malignancies. This study shows that substituting bendamustine for cyclophosphamide in combination with clofarabine and etoposide is safe and effective.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Neoplasias Hematológicas Limite: Adolescent / Child / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Neoplasias Hematológicas Limite: Adolescent / Child / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article