AHOD00P1, a Pilot Study of Re-Induction Chemotherapy with Ifosfamide, and Vinorelbine (IV) in Children with Refractory/Relapsed Hodgkin Disease.

A COG Phase II pilot study was conducted to assess the efficacy of the novel re-induction regimen of ifosfamide/vinorelbine (IV) in pediatric patients with heavily pre-treated relapsed/refractory Hodgkin disease. The treatment regimen consisted of : Ifosfamide 3 gm/m²/d continuous 24-hr IV infusion on Days 1–4; MESNA 3 gm/m²/d continuous 24-hr IV infusion on Days 1–5; and vinorelbine 25 mg/m²/dose IV bolus on Days 1, 5. Filgrastim was administered on Day 6 of Cycle 1 at a dose of 5 μg/kg until ANC ≥ 1000/μl for 3 consecutive days or ≥ 10,000/μl for 1 day and on Day 6 of Cycle 2 at a dose of 10 μg/kg to continue daily until completion of peripheral stem cell mobilization. We report the results of the first phase of the study, that evaluated the re-induction regimen IV which was substantiated as an effective re-induction regimen based on acceptable toxicity profile, capacity to mobilize hematopoietic stem cells (CD34+), and response sufficient to allow subsequent stem-cell transplantation in a large fraction of patients. Twenty-nine patients were accrued on study; 12 male (41%), 17 female (59%); median age at time of enrollment was 16 (range 5–20 yrs). The protocol mandated two cycles of therapy, although some patients received an optional third cycle. This report is based on data from the first 2 cycles only. Twenty-five patients had complete toxicity data. The predominant toxicity was hematologic, specifically leukopenia/neutropenia. The frequencies of grade 3–4 hematologic toxicities included: anemia (62%), leukopenia (100%), neutropenia (95%), and thrombocytopenia (50%). Hypophosphatemia (3%), febrile neutropenia (34.9%) and infection with grade 3 or 4 neutropenia (21.6%), and neurotoxicity (3%), each occurred in a minority of patients. There were no toxic deaths. Harvest was attempted in 25 patients. At least 2.5 x 10⁶ CD34+ cells/kg were collected in 19 (76%), and at least 5.0 x 10⁶ were collected in 16 (64%). Complete response data were available for twenty-five patients. Seven patients attained a complete response (CR) and eleven a partial response (PR) (CR/PR rate 72%). IV was substantiated as an acceptable re-induction regimen for children with Hodgkin disease. It was effective, well tolerated, and allowed for collection of sufficient CD34+ cells to support peripheral stem cell transplantation. Based upon these findings, 35 additional patients will be accrued to more precisely establish the definitive response rate in pediatric patients. In addition, minimally pretreated patients will now be included, allowing assessment of response, toxicity and hematopoietic stem cells (CD34⁺) mobilization in minimally pre-treated patients as well as in the heavily pre-treated population.