AHOD0321: A COG Phase 2 Study of Weekly Gemcitabine and Vinorelbine for Children with Recurrent or Refractory Hodgkin Disease.

Introduction: This COG Phase 2 study was conducted to assess the efficacy and toxicity of gemcitabine and vinorelbine (GV) in pediatric patients with heavily pre-treated relapsed/refractory Hodgkin disease. Both agents have significant single-agent response rates in this setting, and preclinical data suggest the combination will be at least additive.

Methods: GV was given on days 1 and 8 of each 21d treatment cycle: vinorelbine 25 mg/m²/dose IV push and gemcitabine 1000 mg/m²/dose IV over 100 minutes. Filgrastim 5 mg/kg/dose was started on Day 9 and continued for a minimum of 7 days, until the post-nadir absolute neutrophil count was greater than 1500/μL. Response was evaluated after every two cycles. Patients with measurable responses after two cycles were given the option of going off protocol therapy for stem cell transplantation (SCT). A minimum of two additional cycles was mandated for those with stable disease after two cycles. The statistical analysis of response used a two-stage minimax rule to test the null hypothesis that the response rate is ≤40% with 5% Type I error against an alternative hypothesis of a response rate >65%, with 80% power.

Results: Thirty-one eligible patients with a median age of 17.8 years (range 10.7 – 29) were enrolled. Fourteen were female (45%). All patients had received at least 2 prior chemotherapy regimens and 17 had prior autologous SCT. Toxicity and response data are currently available for 24 patients who completed at least two cycles and 16 who completed four cycles of GV. Among those who completed two cycles, hematologic toxicity was predominant, including grade 3–4 anemia (50%), leukopenia (71%), neutropenia (79%), and thrombocytopenia (83%). Nonhematologic grade 3–4 toxicity included elevated SGPT (38%) or SGOT (21%) and hyperbilirubinemia (4%). No patients developed non-cardiogenic pulmonary edema. There have been three documented infectious complications, including febrile neutropenia, sinusitis, and a urinary tract infection. One patient, with a history of prior mediastinal irradiation, developed pericardial and pleural effusions following cycles 4 and 5 of GV, consistent with gemcitabine-induced radiation recall. There were no toxic deaths. Response data are available for 24 patients of whom 18 (75%) have had measurable responses: 5 CRs, 10 VGPRs, and 3 PRs. All radiographic evaluations of treatment response are undergoing centralized review and full response data for all enrolled patients will be available for presentation.

Conclusion: GV is an effective and well-tolerated re-induction regimen for children with relapsed or refractory Hodgkin disease.