A Pilot Study of Sequential Autologous Stem Cell Transplantation and Immunotherapy With Reduced Intensity Allogeneic Stem Cell Transplant for High Risk Neuroblastoma
Despite the modest advances made over the past two decades with the addition of more
intensive chemotherapy and high dose myeloablative therapy with allogeneic or autologous
bone marrow transplantation, children with high-risk neuroblastoma continue to have an
unsatisfactory long-term survival. The current survival for a child > 1 year of age at
diagnosis with stage 4 neuroblastoma is only 20-35% 1,7. The overall treatment plan for
high-risk patients with neuroblastoma will be:
Induction Therapy Intensive induction chemotherapy with the cardioprotectant dexrazoxane
(Zinecard), vincristine, doxorubicin (Adriamycin), and cyclophosphamide (ZVAC), alternating
with cisplatin and etoposide (CiE). Patients who receive induction chemotherapy on an
alternate protocol and achieve a CR, VGPR, or PR will also be eligible for entry to receive
consolidation therapy and AlloSCT immunotherapy after discussion and approval of the
Principal Investigators ).
Consolidation Therapy with AutoSCT Consolidation therapy with a myeloablative preparative
regimen of carboplatin, thiotepa, and topotecan (CaTT) followed by AutoSCT with PBSCs (CD34+
Immunotherapy with Non-myeloablative AlloSCT Immunotherapy with a non-myeloablative
preparative regimen of busulfan and fludarabine followed by AlloSCT with either: (Arm A) a
related donor (5/6 or 6/6 HLA matched); or (Arm B) an umbilical cord blood donor (unrelated
4/6, 5/6, or 6/6 HLA matched, or related 3/6, 4/6, 5/6, or 6/6 HLA matched). Patients with
an umbilical cord blood donor will also receive Thymoglobulin (ATG-rabbit) during the
preparative regimen. GVHD prophylaxis will consist of Tacrolimus and mycophenolate mofetil
Maintenance Therapy Patients with a related donor who have persistent disease detected prior
to NAT/AlloSCT will be assigned to Arm A1 and will receive two courses of DLI, followed by
cis-RA for 6 cycles. Patients with a related donor with no persistent disease detected prior
to NAT/AlloSCT will be assigned to Arm A2 and receive cis-RA for 6 cycles. Patients with an
umbilical cord blood donor will receive cis-RA for 6 cycles.
Radiation Therapy Due to the potential risk of increased GVHD following radiation therapy,
local radiation therapy to the primary tumor site (21 Gy) and metastatic sites, will be
given after NAT/AlloSCT for patients on Arm A2 and Arm B, and prior to cis-RA therapy.
Radiation therapy will be given following DLI in Arm A1, and prior to cis-RA therapy.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To study the feasibility and toxicity of administering sequential MAT/AutoSCT and NAT/AlloSCT in patients with high-risk neuroblastoma.
Darrell Yamashiro, MD
United States: Institutional Review Board
|Columbia Presbyterian Medical Center, Morgan Stanley Children's Hospital New York Presbyterian||New York, New York 10032|